Penta-substituted pyridine compounds, herbicidal compositions and herbicidal method of use

ABSTRACT

Disclosed herein are herbicidal pyridine compounds substituted at the 3- and/or 5-position with a carboxylic acid-derived heterocyclic moiety, as well as herbicidal compositions and use of these compounds.

CROSS-REFERENCE

This application is a continuation-in-part of Ser. No. 07/012,930 filedFeb. 9, 1987, now abandoned.

This invention relates to a new class of 2,6-substitutedpyridinecarboxylic acid derivatives having a wide range of activity asherbicides.

Pyridine derivatives have, for many years, been investigated for use inthe biological sciences. For example,2,6-bis-(trifluoromethyl)-4-pyridinols have been found useful asherbicides and fungicides as disclosed in U.S. Pat. No. 3,748,334. Suchcompounds are characterized by substitution in the 4-position by ahydroxy radical. In addition to the hydroxy radical, the pyridinenucleus may also be substituted with bromo, chloro or iodo radicals.Trifluoromethyl pyridine derivatives have also been disclosed in U.S.Pat. Nos. 2,516,402 and 3,705,170 wherein the nucleus is furthersubstituted by halogens as well as numerous other substituents. Some ofthese compounds are also noted to be useful as herbicides.

Also known because of their fungicidal activity are 4-substituted2,6-dichloro-3,5-dicyanopyridines wherein the 4-position is substitutedwith alkyl, phenyl, naphthyl or pyridyl groups. Such compounds aredisclosed in U.S. Pat. No. 3,284,293, while similar compounds aredisclosed in U.S. Pat. No. 3,629,270 wherein the 4-position issubstituted with a heterocyclic group wherein the hetero atom is oxygenor sulfur.

In EPO patent 44,262 there are disclosed2,6-dialkyl-3-phenylcarbamyl-5-pyridinecarboxylates and5-cyano-compounds useful as herbicides. There is no disclosure of the2-haloalkyl radicals nor any substitution in the 4-position of thepyridine ring.

The pyridine derivatives have also received attention in the search fornew herbicides and have been reported in U.S. Pat. Nos. 1,944,412,3,637,716, and 3,651,070. All of these patents disclose polyhaloderivatives of dicarboxypyridines. All have in common the directsubstitution on a ring carbon by a halogen in the 3- and 5-positionswhile the 2- and 6-positions are occupied by carboxylate groups. The4-position is open to substitution by a wide range of materialsincluding halogens, hydroxy radicals, alkoxy, and carboxyl groups. Suchcompounds have found utilization as herbicides, bactericides, andfungicides. When the 4 position is occupied by a silver salt, U.S. Pat.No. 1,944,412 discloses that such compounds have been utilized in theproduction of X-ray pictures with intravenous injection of suchcompounds.

Pyridinedicarboxylate compounds useful as herbicides are described inEuropean Patent publication No. 133,612 published Feb. 27, 1985 whichcorresponds to U.S. application Ser. No. 602,021. These compounds havefluorinated methyl groups at the 2- and 6-positions and carboxylic acidderivative at the 3- and 5-positions.

Other pyridinedicarboxylate compounds including pyrazole amides aredisclosed in European Patent publication No. 0182769, published May 28,1986. This European publication corresponds to U.S. application Ser. No.768,659.

BRIEF DESCRIPTION OF THE INVENTION

It is an object of this invention to provide herbicidal methods andcompositions utilizing the novel pyridines of this invention.

The novel compounds of this invention are useful as herbicides orintermediates which can be converted to herbicides and are representedby the generic formula ##STR1## wherein:

R₃ is selected from the group consisting of 4,5-dihydro-2-oxazolyl;2-oxazolyl; 2-thiazolyl; 4,5-dihydro-2-thiazolyl;5,6-dihydro-4H-1,3-oxazin-2-yl; 5,6-dihydro-4H-1,3-thiazin-2-yl;4,5-dihydro-1H-imidazol-2-yl; 2-oxazolidinyl; 1,3,4-oxadiazol-2-yl;4,5-dihydro-1,3,4-oxadiazol-2-yl; 1,3-dithiolan-2-yl,1,3-dithian-2-y1,2-thiazolidinyl, 1,3-dioxolan-2-yl, 1,3-dioxan-2-yl,1,3-oxathiolan-2-yl, 5-tetrazolyl, 5-oxazolyl, and the above mentionedheterocycles substituted with one or more substituents selected fromhydrogen, lower alkyl, alkoxy and trifluoroacetyl, and1-amino-4,5-dihydro-1H-imidazolyl;

R₄ is selected from C₁ -C₄ straight or branched chain alkyl, C₃ -C₄cycloalkyl, cycloalkylalkyl, alkylthioalkyl, and bis(alkylthio)alkyl;

R₅ is the same as R₃ or is ##STR2## or --C.tbd.N where Z₁ is O, S, orNR₇ where R₇ is lower alkyl, and Z₂ is selected from alkoxy, alkenoxy,alkynoxy, alkylthio, pyrazolyl, haloalkoxy, cyanoalkoxy, chloro, and--NHR₈ where R₈ is lower alkyl; and

R₂ and R₆ are independently selected from fluorinated methyl,chlorofluorinated methyl, chlorinated methyl and lower alkyl, providedthat one of R₂ and R₆ must be fluorinated or chlorofluorinated methyl;

provided that R₃ is not 4,5-dihydro-1-methyl-1H-imidazol-2-yl when R₅ ismethylthiocarbonyl, and R₃ is not an unsubstituted4,5-dihydro-1H-imidazol-2-yl when R₅ is methoxycarbonyl.

The term "alkyl" means herein both straight and branched chain radicalswhich include, but are not limited to, ethyl, methyl, n-propyl,1-ethylpropyl, 1-methylpropyl, n-butyl, 2,2-dimethylpropyl, pentyl,isobutyl, isopropyl.

The term "lower alkyl" herein means an alkyl radical having 1 to 7carbon atoms. The terms "lower alkenyl" and "lower alkynyl" herein meanalkenyl and alkynyl groups having 3 to 7 carbon atoms. Examples of suchalkenyl groups include 2-propenyl, 2-butenyl, 3-butenyl,2-methyl-2-propenyl, and the like. Examples of such lower alkynyl groupsinclude 2-propynyl, and so forth.

The term "cycloalkylalkyl" means a C₁ -C₂ alkyl group substituted with aC₃ -C₆ cycloalkyl group, such as cyclopropylmethyl, cyclopropylethyl,cyclobutylmethyl, cyclopentylethyl, and so forth.

The terms "fluorinated methyl", "chlorinated methyl", and"chlorofluorinated methyl" mean methyl radicals wherein one or more ofthe three hydrogen atoms have been replaced by a fluorine atom, achlorine atom, or a fluorine atom and a chlorine atom, respectively.

DETAILED DESCRIPTION OF THE INVENTION

The novel herbicidal derivative and their compounds of this inventionare readily prepared by reaction of a pyridinedicarboxylic acid monoester, monoacid halide or a diacid halide with a γ-hydroxyamine having2-3 carbon atoms or a hydrazine having one carbon atom to form thepyridinedicarboxylic acid amide, bis-amide, or hydrazide respectively.Steps 1-9 which follow set out in detail the preparation of threespecific acid halides which are used as starting materials for thecompounds of this invention. Other acid halides may be readily preparedusing the procedures of Steps 1-9 by varying the ketoester and aldehydeused in Step 1 to obtain the desired substituents in thepyridinedicarboxylate product. Other suitable pyridinedicarboxylic acidhalides as starting materials are shown in European Patent publicationNo. 133,612 and U.S. Pat. No. 4,692,184 in Examples 44-51 and 82-83inclusive, and halide starting materials used herein are generallyprepared using the techniques set out in that European Patentpublication.

The following Steps 1-9 illustrate an example of the procedures forpreparation of the acid halide compounds which are the startingmaterials for making the compounds of the present invention. In thesesteps, a β-ketoester is reacted with an aldehyde preferably usingpiperidine as a catalyst to form a pyran (Step 1). The pyran is thenreacted with ammonia to form a dihydroxypiperidine (Step 2), which isdehydrated to make a dihydropyridine compound (Step 3). Thedihydropyridine is then oxidized or dehydrofluorinated to prepare apyridinedicarboxylate compound (Step 4). In the dehydrofluorinationstep, an organic base such as DBU (hereinafter defined) is employed.

The ester groups of the pyridinedicarboxylate compound are the estergroups of the β-ketoester, and the 4-position of the pyridine issubstituted with the aldehyde substituent.

When the pyridinedicarboxylate is substituted at the 2- or 6-positionwith a trifluoromethyl radical and at the other of these positions witha difluoromethyl hydrolysis of the pyridinedicarboxylate compound occursselectively on the side having the CF₂ H group when one equivalent of abase such as KOH is employed in the hydrolysis (Step 8). When twoequivalents of base or more are employed, the dicarboxylate ishydrolyzed to the diacid (Step 5). The diacid may be converted to thediacid chloride by treatment with a chlorinating agent such as SOCl₂ orPCl₅. Following this conversion, treatment with one equivalent of analcohol selectively esterifies the diacid chloride on the chloride groupadjacent the CF₂ H group.

The novel compounds of this invention wherein one of the R₃ or R₅ is a2-oxazolidinyl, 2-thiazolidinyl, 1,3-dithiolan-2-yl, and1,3-dithian-2-yl can be prepared from the corresponding 3- or 5-formylderivatives. Step 10 and Step 11 set out in detail the preparation ofthe formyl derivatives.

STEP 1

Preparation of dimethyl2,6-bis(trifluoromethyl)-2,6-dihydroxy-4-isobutyl-tetrahydro-3,5-pyrandicarboxylate.

To a mechanically stirred mixture of 280 g (2.0 mole) of 80% pure methyltrifluoroacetoacetate and 86 g (1.0 mole) of isovaleraldehyde is added 1ml of piperidine. An exothermic reaction occurs and the temperature ofthe reaction mixture reaches 105° C. After 5 hours of stirring, thereaction mixture is triturated with 450 ml of hexane and 30 ml of etherand cooled with a dry ice bath to give 1.68 g of a first crop, m.p.83°-87° C. and 14.51 g of a second crop, m.p. 67°-73° C.

The first crop is the desired product which contains a mixture of 5:1cis and trans isomers.

Anal. Calc'd for C₁₅ H₂₀ F₆ O₇ : C, 42.26; H, 4.73 Found: C, 42.54; H,4.77.

The second crop is a 2:1 mixture of cis and trans isomers. The motherliquor is concentrated to give 344 g of a residue which is a crudemixture of cis and trans isomer of the desired product.

STEP 2

Preparation of dimethyl2,6-bis(trifluoromethyl)-2,6-dihydroxy-4-isobutyl-3,5-piperidinedicarboxylate.

To a solution of 344 g (0.920 mole) crude product from Step 1 in 500 mlof tetrahydrofuran (THF) is passed 58 g (3.41 mole) of gaseous ammoniafor 3 hours. The reaction mixture is concentrated and the residue (332g) is recrystallized from hexane-ether to give 53.7 g (13% yield frommethyl trifluoroacetoacetate) of the desired product as a white solid,m.p. 102°-106° C.

Anal. Calc'd for C₁₅ H₂₁ F₆ N₁ O₆ : C, 42.36; H, 5.00; N, 3.29 Found: C,42,84; H, 4.94; N, 3.29.

The mother liquor is concentrated to provide more of the crude desiredproduct.

STEP 3 Preparation of a 2:1 mixture of dimethyl2,6-bis(trifluoromethyl)-1,4-dihydro-4-isobutyl-3,5-pyridinedicarboxylate and its 3,4-dihydropyridine isomer.

Method A: To an ice water cooled mixture of 200 ml of concentratedsulfuric acid and 200 ml of methylene chloride is added 48.7 g (0.115mole) of the product of Step 2 at once. The reaction mixture is stirredfor 20 minutes and poured into 1 L. of ice water. The methylene chloridelayer is separated and washed once with 100 ml of saturated sodiumbicarbonate, dried and concentrated to give 28.0 g (64.6%) of crudeproduct. A portion (5.0 g) of this product is kugelrohr distilled at 0.5torr (pot temperature at 120° C.) to give 4.8 g of the desired product,n_(D) ²⁵ 1.4391.

Anal. Calc'd for C₁₅ H₁₇ F₆ O₄ : C, 46.28; H, 4.40; N, 3.60; Found: C,46.39; H, 4.44; N, 3.60.

Method B: To a mechanically stirred mixture of 340.3 g (1.98 mol) of98.9% pure methyl trifluoroacetoacetate (MTFAA), 100 mL of toluene and0.86 g (0.01 mol) of piperidine was added 90.5 g (1.03 mol) ofiso-valeraldehyde in 20 minutes. The reaction mixture exothermed causinga rise of temperature of 83° C. The reaction mixture was maintained at80° C. for 3 hours. ¹⁹ F NMR showed that the reaction was 89% complete.Heat was removed, and the reaction mixture was diluted with 125 mL oftoluene and stirred overnight (16 hours). Gaseous ammonia was passedthrough the reaction, the exotherm caused a rise of temperature to 68°C. in 50 minutes. A water cooling bath was applied to the reactionvessel to reduce the reaction temperature to 53° C. while ammonia waspassed continuously. A total of 47.3 g (2.78 mol) of ammonia was passedin 1.5 hours. ¹⁹ F NMR indicated that dimethyl2,6-bis(trifluoromethyl)-2,6-dihydroxy-4-isobutyl-3,5-piperidinedicarboxylateconstituted 91% of the product mixture. The reaction mixture was dilutedwith 100 mL of toluene. A Claisen distillation head was attached to thereaction vessel.

Excess ammonia and parts of toluene were removed in vacuo (wateraspirator) while temperature was maintained at 26° C. An additional 200mL of toluene was added, and the distillation was continued to remove atotal of 200 mL of distillate in 1.5 hours. The reaction mixture wasdiluted with 100 mL of toluene and cooled to 5° C. with an ice bath.Sulfuric acid (453 g, 4.53 mol) was added in 5 minutes. The exothermcaused the temperature to rise to 25° C. The temperature graduallysubsided to 5° C. in 10 minutes and was maintained at 5° C. for 40minutes. An additional 95 g (0.95 mol) of sulfuric acid was added, andthe reaction mixture was stirred at 5° C. for 20 minutes before beingpoured into a mixture of 500 mL of toluene and 2 L of ice water. Thetoluene layer was separated and the aqueous layer was extracted oncewith 500 mL of toluene. The combined toluene extracts were washedsuccessively with 500 mL of water, 500 mL of saturated aqueous NaHCO₃,500 mL of brine and concentrated in vacuo to 363.6 g of an oil. GC areapercentage analysis indicated that the oil contained 9% of dimethyl2,6-bis(trifluoromethyl)-3,4-dihydro-4-isobutyl-3,5-pyridinedicarboxylateand 75.4% of dimethyl2,6-bis(trifluoromethyl)-1,4-dihydro-4-isobutyl-3,5-pyridinedicarboxylatecorresponding to an overall yield of 82.5% from MTFAA.

STEP 4 Preparation of dimethyl2-(difluoromethyl)-6-(trifluoromethyl)-4-isobutyl-3,5-pyridinedicarboxylate

(a) Reaction of the Product of Step 3 with DBU

A mixture of 23.0 g (0.0591 mole) of the product of Step 3, 12.2 g(0.077 mole) of 96% pure DBU, and 100 ml of THF is held at reflux for 3days and poured into 250 ml of 3N HCl. The oil precipitate is extractedinto ether (2×100 ml). The ether extracts are dried (MgSO₄) andconcentrated to give 14.4 g of an oil which, according to ¹ H NMR,contained the desired product and acidic products. This oil is dissolvedin ether and extracted with 100 ml of saturated sodium bicarbonate. Theether layer is dried (MgSO₄) and concentrated to give 8.9 g of an oilwhich is the desired product (7% pure by .sup.· F NMR).

The sodium bicarbonate extract is acidified with concentrated aqueousHCl to give an oil which is extracted into ether. The ether layer isdried (MgSO₄) and concentrated to give 4.8 g of a residue whichcontained monocarboxylic acid and dicarboxylic acid (9:1) derived fromthe desired product. This residue is treated with 3.0 g (0.0217 mole) ofpotassium carbonate, 20 ml of methyl iodide, and 50 ml of acetone. Themixture is held at reflux for 42 hours and concentrated. The residue istreated with water and extracted with ether (2×100 ml). The ether layeris dried and concentrated. The residue is kugelrohr distilled at 1 torr(pot temperature at 130° C.) to give 5.1 g (23.4% from Step 3) of thedesired product as an oil, n_(D) ²⁵ 1.4478. This product crystallizesafter standing, m.p. 36°-37° C.

Anal. Calc'd for C₁₅ H₁₆ F₅ N₁ O₄ : C, 48.79; H, 4.37; N, 3.79; Found:C, 48.75; H, 4.39; N, 3.77.

The 71% pure desired product described previously was chromatographed byHPLC using 3% ethyl acetate/cyclohexane as eluent to give an earlierfraction (0.79 g, retention time 7-8.5 minutes) which was identified asmethyl6-(difluoromethyl)-4-(isobutyl)-2-(trifluoromethyl)-3-pyridinecarboxylate.The second fraction (retention time 8.5-18.5 minutes) is an additional6.4 g (29.4%) of pure desired product, n_(D) ²⁵ 1.4474.

(b) Reaction of the Product of Step 3 with Tributylamine

A mixture of 38.9 g of an 80% pure product of Step 3 and 20.5 g oftributylamine is heated to 155° C. in 30 minutes. The reaction mixturewas cooled to 30° C. and diluted with 100 ml of toluene. The toluenesolution is washed successively with 6N hydrochloric acid, saturatedsodium bicarbonate, and brine, dried and concentrated to give 36.4 g ofa 73% pure product which corresponds to an 86% yield. This reaction canalso be carried out in excess of tributylamine (10 equivalent) givingessentially similar results.

(c) Reaction of the Product of Step 3 with Tributylamine in Toluene

A mixture of 38.9 g of an 80% pure product of Step 1, 20.4 g oftributylamine and 30 ml of toluene is heated to 115° C. in 40 minutesand held at 115° C. for 1 hour and 40 minutes. The reaction mixture iscooled and worked up as in (b) above to give 36.3 g of a 76% pureproduct which corresponds to a 90% yield.

(d) Reaction of the Product of Step 3 with Triethylamine

A mixture of 11.8 g of an 80% pure product of Step 3 and 3.34 g oftriethylamine is heated at 100° C. for 10 minutes, then at 125° C. for10 minutes. The reaction mixture was cooled and worked up as in (b)above to give 8.14 g of a 76% pure product which corresponds to a 63%yield.

(e) Reaction of the Product of Step 3 with 2,6-Lutidine in the Presenceof a Catalytic Amount of DBU

A mixture of 5.0 g of product of Step 3 and 2.13 g of 2,6-lutidine isheated at 143° C. for 30 minutes. Two drops of DBU are added and thereaction mixture is heated for additional 1 hour and 30 minutes, cooledand worked up as in (b) above to give 4.23 g of the desired product. Thereaction can also be carried out in excess of 2,6-lutidine and acatalytic amount of DBU without solvent or in the presence of toluene assolvent giving similar results.

STEP 5 Preparation of2-(difluoromethyl)-6-(trifluoromethyl)-4-isobutyl-3,5-pyridinedicarboxylicacid.

A 5-liter flask was charged with 894 g (2.42 mol) of the compound ofStep 4 and 1 liter of water. To this was added a solution of 574 g (8.7mol) of KOH in 800 ml of water. The mixture was refluxed overnight,after which HPLC showed that the reaction was complete. The flask wascooled to room temperature, acidified with aqueous HCl, and stirreduntil the organic phase solidified. The solids were filtered, washedwith water, and dried in a fluid bed dryer. The diacid was obtained (756g, 91.6% yield) as a brown solid.

STEP 6 Preparation of3,5-bis-chlorocarbonyl-2-difluoromethyl-4-isobutyl-6-trifluoromethyl-pyridine

The diacid product of Step 5 (37.06 g, 0.108 mole) was refluxed with 150ml SOCl₂ for three hours. At this time, ¹⁹ F NMR indicated the reactionwas complete. The excess SOCl₂ was removed by rotary evaporation,leaving a dark oil which was the bis-acid chloride. This was Kugelrohrdistilled at 100° C. to give a colorless oil.

STEP 7 Preparation of methyl5-chlorocarbonyl-2-difluoromethyl-4-isobutyl-6-trifluoromethyl-pyridine-3-carboxylate

The product of Step 6 was then dissolved in 100 ml THF followed by 100ml methanol. After 21/2 hours the solvent was evaporated, leaving 31.2 gwhite solid, m.p. 71°-75° C. in 77% yield.

STEP 8 Preparation of2-difluoromethyl-4-isobutyl-6-trifluoromethyl-3,5-pyridinedicarboxylicacid, 5-methyl ester

A 1-liter 4-necked flask was charged with 300 gm of product of Step 4and about 200 ml ethanol. In a separate flask was combined 59.14 g(0.896 mol) of 85% KOH and about 100 ml of water. The aqueous solutionwas poured into the organics and the flask was equipped with amechanical stirrer, thermometer, nitrogen inlet and a water cooledcondenser. The reaction mixture was heated to reflux for 45 minutes andwas cooled. The reaction mixture was concentrated and then diluted withwater and washed once with ethyl ether. The ether wash (to removestarting material) was discarded. The aqueous solution was acidifiedwith concentrated aqueous HCl and the orange precipitate that resultedwas extracted with ethyl ether. (The aqueous solution was extracted atotal of 3 times because of the volume.) The ether extracts werecombined and dried over anhydrous magnesium sulfate, filtered andconcentrated to yield 253.13 gm (87.53% yield) of the monoacid acid.

STEP 9 Preparation of methyl 2-difluoromethyl-3-chlorocarbonyl-4-isobutyl-6-trifluoromethyl-5-pyridinecarboxylate

The acid (253 g 0.7121 mol) from Step 8 was refluxed for 24 hours inapproximately 250-300 ml of thionyl chloride. The reaction mixture wasconcentrated to yield 244.59 gms. of acid chloride in 91.90% yield.n_(D) ²⁵ 1.4614.

STEP 10 3-pyridinecarboxylic acid,2-(difluoromethyl)-5-(hydroxymethyl)-4-(2-methylpropyl)-6-(trifluoromethyl),methyl ester

To a mixture of 14.2 g (0.64 mol) of sodium borohydride and 700 mL ofdiglyme cooled in an ice-water bath was added a solution of 118.5 g(0.32 mol) of methyl5-(chlorocarbonyl)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylatein 200 mL of diglyme at a fast dropwise pace. The reaction wasexothermic during addition of the acid chloride solution. After theaddition was complete, the reaction mixture was stirred in the ice-waterbath for 1 hour then at room temperature for 2 hours. At this point GCshowed that the reaction was complete. To the above reaction mixture wasadded very slowly 150 mL of concentrated hydrochloric acid causingvigorous evolution of gas. After gas evolution had subsided the reactionmixture was concentrated in vacuo (0.1 torr) at 75° C. The residual oilwas taken up in 300 mL of CH₂ Cl₂ and washed with 300 mL of water. TheCH₂ Cl₂ layer was dried (MgSO₄) and concentrated in vacuo. The residuewas Kugelrohr distilled at 110° C. (0.04-torr) to remove diglyme. Theresidue was chromatographed by HPLC using hexane: CH₂ Cl₂ : EtOAc(10:1:1, v/v) as eluent to give 93.6 g (85.8%) of light yellow solid, mp65°-67° C.

STEP 11 3-pyridinecarboxylic acid,2-(difluoromethyl)-5-formyl-4-(2-methylpropyl)-6-(trifluoromethyl),methyl ester

To a suspension of 14.2 g (0.0655 mole) of pyridinium chlorochromate in60 ml of CH₂ Cl₂ was added 14.9 g of product of Step 10 in 40 ml of CH₂Cl₂. The mixture was stirred at room temperature overnight and dilutedwith 400 ml of ether and filtered through a short pad of silica geltwice to give a light brown solution, which was concentrated to give13.9 g of a residue and then purified by HPLC (3% ethylacetate/cyclohexane) to give 12.75 g of a light yellow oil, n_(D) ²⁵1.4564.

In compounds of this invention wherein R₅ is a dihydro-oxazole ordihydro-oxazole derivative, the acid halide prepared as in one of Steps6, 7 or 9 is reacted with a 2-hydroxyethyl amine to form thecorresponding 2-hydroxyethyl amide. The amide is treated in a suitablesolvent (such as CH₂ Cl₂ or the like) with a chlorinating agent (SOCl₂,PCl₅, etc.) to form the corresponding α-chloroethyl amide, which is thencyclized with a suitable base such as potassium t-butoxide (t-BuOKhereinafter) to form the dihydrooxazole or dihydro-oxazole derivative.

Dihydrothiazole compounds of this invention and their derivatives areformed by treatment of the 2-hydroxyethylamide above with P₂ S₅ to forma carbothioamide which cyclizes to the dihydrothiazole. Treatment of the2-hydroxyethyl amide above with P₂ S₅ and hexamethyl phosphoramideresults in sulfurization and cyclization to form the4,5-dihydrothiazole.

Oxadiazole compounds of this invention are formed by reaction of ahydrazine with the acid chloride to make a hydrazide, followed bycyclization.

Imidazole compounds are prepared by reaction of a 2-chloroethyl amidewith phosphorus pentachloride followed by reaction of the intermediatewith ammonia or an alkylamine.

Six-membered ring counterparts of the above pyridines with 5-memberedring substitution are prepared by cyclization of 3-chloropropyl amides.

Preparation of compounds of this invention will become clear byreference to the following examples.

As used throughout the specification, including the Examples, thefollowing abbreviations have the following meanings:

THF--tetrahydrofuran

HPLC--high pressure liquid chromatography

TLC--thin layer chromatography

RT--room temperature

DBU--1,8-diazabicyclo-[5.4.0]-undec-5-ene

HMPA--hexamethyl phosphoramide

EtOAc--ethyl acetate

DME--dimethoxyethane

t-BuOK--potassium t-butoxide

EXAMPLE 1 3-pyridinecarboxylic acid,6-(difluoromethyl)-5-(4,5-dihydro-4-methyl-1,3,4-oxadiazol-2-yl)-4-(2-methylpropyl)-2-(trifluoromethyl),-methylester

3-pyridinecarboxylic acid,5-chlorocarbonyl-6-(difluoromethyl)-4-(2-methylpropyl)-2-(trifluoromethyl)-,methyl ester (2.28 g=0.0061 mole) and 30 ml CH₂ Cl₂ were cooled in anice bath before adding 0.8 ml NH₂ NHCH₃. The reaction mixture becamecloudy white. After 40 minutes the ice bath was removed. One hour latera gas chromatographic assay showed complete reaction. The mixture waswashed with H₂ O and extracted with CH₂ Cl₂. The CH₂ Cl₂ layer was driedwith MgSO₄, filtered and concentrated to 2.2 g white solid. This wasrecrystallized from about 30% ethyl acetate/hexanes to give 1.5 g3,5-pyridinedicarboxylic acid,2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,3-(2-methylhydrazide) 5-methyl ester as a fluffy white solid. m.p.155°-159° C. Also, 0.9 g of this intermediate was recovered from thefiltrate.

The hydrazide (2.4 g), 27 ml 95% HCOOH and 25 ml 37% formaldehyde werecombined at room temperature. The reaction was homogeneous. After 1 hour¹⁹ F Nmr showed one major CF₃ peak. The reaction sat overnight at roomtemperature with no major change in the ¹⁹ F NMR spectrum. The mixturewas poured into ice/H₂ O and extracted with CH₂ Cl₂. The CH₂ Cl₂ layerwas washed with NaHCO₃ (aqueous) and then dried with MgSO₄, filtered andconcentrated to 2.5 g colorless oil. This was chromatographed in 30% CH₂Cl₂ /cyclohexane, gradually increasing to 100% CH₂ Cl₂. The product(1.56 g) was recovered as a colorless oil, n_(D) ²⁵ =1.4822 (63% yield).

EXAMPLE 2 3-pyridinecarboxylic acid,6-(difluoromethyl)-5-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester

A solution of 4.2 ml of dimethylethanolamine (0.044 mole) and 25 ml CH₂Cl₂ was cooled by an ice bath under a N₂ atmosphere. Then a solution of16.53 g acid chloride used in Example 1 (0.044 mole) in 100 ml CH₂ Cl₂was added over a 50 minute period. The bath was removed and stirring wascontinued at room temperature. Another 4 ml of dimethylethanolamine wasadded, and the reaction stirred over the weekend. There was solid in thereaction mixture. It was washed with diluted aqueous HCl and extractedwith CH₂ Cl₂. The CH₂ Cl₂ layer was dried with MgSO₄, filtered andconcentrated to 18.36 g orange solid. This was purified by chromatographusing 40% EtOAc/cyclohexane. About 5 g good product was recovered, alongwith some impure product. The best material was recrystallized from 35%EtOAc/hexane to give 2.9 g white solid. m.p. 170°-173°. The impureproduct was further purified by boiling in 10% EtOAc/hexane andfiltering off the insoluble amide. A total of 7.0 g of3-pyridinecarboxylic acid,6-(difluoromethyl)-5-[[(2-hydroxy-1,1-dimethylethyl)amino]carbonyl]-4-(2-methylpropyl)-2-(trifluoromethyl)-,methyl ester was prepared in this manner (37% yield).

This hydroxyethyl amide compound (3.65 g=0.0086 mole) was heated with 30ml SOCl₂ for approximately 13/4 hours. ¹⁹ F NMR showed the reaction wascomplete. The SOCl₂ was evaporated, leaving a white solid. This wasdissolved in CH₂ Cl₂ and washed with H₂ O. The CH₂ Cl₂ layer was driedwith MgSO₄, filtered and concentrated to yield 3-pyridinecarboxylicacid,5-[[(2-chloro-1,1-dimethylethyl)amino]carbonyl]-6-(difluoromethyl)-4-(2-methylpropyl)-2-(trifluoromethyl)-,methyl ester as a solid (3.4 g). This 89% yield was recrystallized from5% EtOAc/hexane. m.p. 136°-138° C.

This intermediate (2.46 g=0.0055 mole) and 90 ml dry THF were combinedunder N₂ and cooled in an ice bath. Then 0.70 g t-BuOK was added (0.0062mole). The reaction mixture turned dark in color. After 1 hour the THFwas evaporated, and the residue was washed with H₂ O and extracted withether. The ether layer was dried with MgSO₄, filtered and concentratedto 2.36 g orange oil. This was purified by chromatograph using 5%EtOAc/cyclohexane and then Kugelrohr distilled at 110° C. to give 1.29 gcolorless oil. (57% yield) It gradually solidified. m.p. 69°-71° C.

EXAMPLE 3 3-pyridinecarbothioic acid,6-(difluoromethyl)-5-(4,5-dihydro-2-oxazolyl)-4-(2-methylpropyl)-2-(trifluoromethyl)-,S-methyl ester

A solution of 2.5 ml ethanolamine (0.0394 mole) in 50 ml CH₂ Cl₂ wascooled by an ice bath before adding 7.28 g of 3-pyridinecarbothioicacid,5-(chlorocarbonyl)-6-(difluoromethyl)-4-(2-methylpropyl)-2-(trifluoromethyl)-,S-methyl ester (0.0187 mole) in 70 ml CH₂ Cl₂ dropwise. The bath wasremoved and the mixture was stirred magnetically for 2 hours. Thereaction sat overnight before workup. It was washed with NaCl(aqueous)and extracted with more CH₂ Cl₂. The CH₂ Cl₂ layer was collected, driedwith MgSO₄, filtered and concentrated to an orange oil. This wasdissolved in ethyl acetate and filtered through silica gel. Afterconcentrating, 6.44 g was recovered. 83% yield. A 1.4 g sample waschromatographed in 40% EtOAc/cyclohexane. A pale colored oil (1.16 g)was recovered which gradually solidified. This was recrystallized from10% EtOAc/hexanes. There was recovered 0.92 g of 3-pyridinecarbothioicacid,6-(difluoromethyl)-5-[[(2-hydroxyethyl)amino]carbonyl]-4-(2-methylpropyl)-2-(trifluoromethyl)-,S-methyl ester as white crystals: m.p. 102°-106° C.

This material (5.31 g=0.0128 mol) was combined with 50 ml SOCl₂ at roomtemperature. The reaction was followed by ¹⁹ F NMR. After 21/2 hours ¹⁹F NMR showed two CF₂ peaks. The solution was refluxed for 40 minuteswith no change in the spectrum. The reaction sat overnight at roomtemperature. The SOCl₂ was rotavapored off, leaving a yellow solid. Thiswas dissolved in ether and washed with H₂ O. The ether layer wascollected, dried with MgSO₄, filtered and concentrated to a 5.0 g yellowsolid. This was recrystallized from 10% EtOAc/cyclohexane which yielded3.4 g (60% yield) white solid. ¹⁹ F NMR spectrum showed one singlet forthe CF₃. The filtrate showed two components of which one was3-pyridinecarbothioic acid,5-[[(2-chloroethyl)amino]carbonyl]-6-(difluoromethyl)-4-(2-methylpropyl)-2-(trifluoromethyl)-,S-methyl ester. The identity of the other component is unknown.

This intermediate (2.40 g=0.0055 mole) was dissolved in dry THF under aN₂ atmosphere. The solution was cooled in an ice bath before adding 0.76g t-BuOK (0.0068 mole). The solution immediately darkened in color.After 10 minutes the ice bath was removed and the solution warmed toroom temperature. A gas chromatographic assay showed complete reaction,so it was poured into water and extracted with ether. The ether layerwas collected, dried with MgSO₄, filtered and concentrated to 2.02 gyellow oil which began to solidify. It was chromatographed in 20%EtOAc/cyclohexane and then recrystallized from hexane to give 1.70 gproduct (77% yield). m.p. 88°-90° C.

EXAMPLE 4 3-pyridinecarboxylic acid,6-(difluoromethyl)-5-(5-methoxy-2-oxazolyl)-4-(2-methylpropyl)-2-(trifluoromethyl)-,methyl ester

The acid chloride starting material of Example 1 (12.81 g=0.0345 mole)was dissolved in 100 ml CH₂ Cl₂. To this solution was added 4.68 g(0.0373 mol) of glycine methyl ester hydrochloride. This mixture wascooled in an ice bath before adding 10 ml of ethyldiisopropylamine(EDPA)(0.0574 mole) by pipet. The ice bath was removed, and the reactionstirred overnight at room temperature. ¹⁹ F NMR showed the reaction wasincomplete. An additional 3 ml of EDPA (0.0172 mol) was added. After 1/2hour a gas chromatographic assay showed complete reaction. It was washedwith dilute HCl and extracted with CH₂ Cl₂. The CH₂ Cl₂ layer was driedwith MgSO₄, filtered and concentrated to 14.2 g orange oily solid. Twograms were chromatotroned (20% EtOAc/cyclohexane) and thenrecrystallized to give 1.2 g of 3-pyridinecarboxylic acid,6-(difluoromethyl)-5-[[(2-methoxy-2-oxoethyl)amino]carbonyl]-4-(2-methylpropyl)-2-(trifluoromethyl)-,methyl ester as a white solid. m.p. 126°-129° C.

This material (8.90 g=0.0209 mole), 85 ml of CCl₄ and 4.5 g of PCl₅(0.0216 mole) were combined and heated at reflux for one hour. NMRshowed complete reaction to the intermediate. The cyclization reactionwas accomplished by three different procedures.

1. About 10 ml of the intermediate solution was evaporated to removeCCl₄ and POCl₂ and then heated at 50° C. on the Kugelrohr apparatus toremove trace components. The residue was dissolved in CH₂ Cl₂ and thenwashed with NaHCOs(aqueous). The CH₂ Cl₂ layer was dried with MgSO₄,filtered and concentrated to a yellow oil. This procedure effected nochange in the NMR. The oil was dissolved in 25 ml xylene and refluxedfor 2 hours. The reaction was followed by NMR. When it indicated thereaction was complete, the xylene was evaporated to give the oxazole asa yellow oil.

2. About 10 ml of the intermediate solution was evaporated and thenheated on the Kugelrohr apparatus at 100° C. After 15 minutes a gaschromatographic assay of the pot contents showed partial reaction to theoxazole. The reaction was heated at 100° C. for another hour but a gaschromatographic assay still showed some intermediate. Then heating wasresumed up to 135° C. and the oxazole distilled over.

3. The remaining intermediate solution was evaporated and heated on theKugelrohr apparatus at 50° C. for a short time to remove traces of CCl₄/POCl₃. The residue was dissolved in xylene and refluxed overnight (17hours). NMR showed complete reaction. The xylene was evaporated and thedark residue was Kugelrohr distilled. There was 3.3 g of pale orange oilcollected.

All three oxazole products were combined and purified by chromatography(10% EtOAc/cyclohexane) and then Kugelrohr distilled. The product (4.58g) was recovered as a colorless oil. n_(D) ²⁵ =1.4836 (54% yield)

EXAMPLE 5 3-pyridinecarboxylic acid,6-(difluoromethyl)-4-(2-methylpropyl)-5-(2-thiazolyl)-2-(trifluoromethyl)-,methyl ester

Several experiments were run in an attempt to work out a procedure forthe preparation of this compound. All gave a low yield of the thiazole.It was found that an intermediate of unknown identity, when pyrolyzed,yielded the thiazole. The following is an example of one experiment.

3-pyridinecarboxylic acid,6-(difluoromethyl)-5-[[(2,2-dimethoxyethyl)amino]carbonyl]-4-(2-methylpropyl)-2-(trifluoromethyl)-,methyl ester prepared from the acid halide used in Example 1 (11.36g=0.0257 mole), 100 mole toluene and 5.89 g P₂ S₅ (0.0265 mol) wererefluxed together for approximately 3 hours. The reaction was followedby gas chromatography and the assays showed the thiazole to be present.It was washed with NaHCO₃ (aqueous) and extracted with ether. The etherlayer was dried with MgSO₄, filtered and concentrated to 12.88 g glassyorange solid. TLC shows a lot of material at the origin when using 5%EtOAc/cyclohexane. An attempt was made to chromatograph the crudeproduct in this solvent system but it would not dissolve. The liquidphase was decanted and then purified by liquid chromatography. Only 0.4g product was recovered. The insoluble material was shown by gaschromatography to contain the thiazole but TLC did not detect it. Atthis point it became apparent that a reaction was occurring on the gaschromatographic column. A small sample was heated in a capillary tube to240° C. and then assayed by TLC. This showed thiazole was formed bypyrolysis. An empty flask was heated by a mantle to an air temperatureof 180° C. and then approximately 3 g of glassy solid intermediate wasadded. After a few seconds it had turned very dark so the heat sourcewas removed. The dark residue contained thiazole as shown by TLC. It wasKugelrohr distilled at 130° C. and then chromatographed in 10%EtOAc/cyclohexane to give 0.7 g yellow solid. (11% yield) This materialwas combined with products from other experiments, purified bychromatography in 10% EtOAc/cyclohexane and Kugelrohr distilled at 120°C. to give 1.60 g of product as a yellow solid. m.p. 71°-75° C.

EXAMPLE 6 Pyridine,2-(difluoromethyl)-3,5-bis(4,5-dihydro-2-oxazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-

Pyridine,3,5-bis(chlorocarbonyl)-6-difluoromethyl-4-(2-methylpropyl)-2-(trifluoromethyl)(8.25 g=0.022 mole) and 70 ml CH₂ Cl₂ were combined and cooled in an icebath before adding in 6 ml (0.099 mol) of ethanolamine. A precipitateformed immediately. After 15 minutes the ice bath was removed. Themixture was stirred for 2 hours at room temperature. The CH₂ Cl₂ layerwas assayed by ¹⁹ F NMR which showed no pyridine product to be present.Therefore, the product was insoluble in CH₂ Cl₂. The reaction mixturewas washed with H₂ O and extracted twice with ethyl acetate. The ethylacetate layer was dried with MgSO₄, filtered and concentrated to 8.78 gof white solid. (94% yield)

The bis-hydroxyethylamide (2.67 g=0.0062 mole) and 40 ml POCl₃ wererefluxed together for approximately 31/2 hours. The POCl₃ was evaporatedand the residue was washed with H₂ O and extracted with EtOAc. The EtOAclayer was dried with MgSO₄, filtered and concentrated to 2.58 g of tansolid (90% yield). A small sample was purified by chromatography in 20%EtOAc/cyclohexane to give 3,5-pyridinedicarboxamide,N,N'-bis(2-chloroethyl)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-as a white solid. m.p. 266°-268° C.

This intermediate (2.18 g=0.0047 mole) and 50 ml dry THF were combinedand cooled in an ice bath before adding 1.13 g of t-BuOK (0.0101 mole).There was a slight color change and a precipitate noted. After 1/2 hourthe ice bath was removed. ¹⁹ F NMR and gas chromatography showedcomplete reaction. The reaction ether. The ether layer was dried withMgSO₄, filtered and concentrated to 2.0 g pale yellow solid. This waspurified by chromatography in 50% EtOAc/cyclohexane to give 1.8 g ofsolid. This was recrystallized from hexanes to give 1.2 g of product ascream-colored crystals (65% yield). m.p. 138°-144° C.

EXAMPLE 7 Pyridine,2-(difluoromethyl)-3,5-bis(4,5-dihydro-2-thiazolyl)-4-(α-methylpropyl)-6-(trifluoromethyl)-

The bis-hydroxyethylamide prepared in the first step of Example 6 (7.65g=0.018 mole), 10 ml HMPA, 60 ml of xylene and 4.03 g of P₂ S₅ (0.018mole) were combined and heated at reflux for approximately 31/2 hours.After this time the reaction showed two liquid phases. Then 4.1 g of P₂S₅ was added and reflux continued for another hour. The mixture remainednon-homogeneous. It was cooled and then filtered through silica gelusing 30% EtOAc/cyclohexane. A yellow oil was recovered (8.5 g) whichstill contained some HMPA by ¹ H NMR. This material was purified bychromatography using 20% EtOAc/cyclohexane. About 3 g of a yellow solidwas recovered. This was recrystallized twice from hexane to give 1.7 gof the product as white crystals. m.p. 134°-136° C. (22% yield)

EXAMPLE 8 Pyridine,4-cyclobutyl-2-(difluoromethyl)-3,5-bis(4,5-dihydro-2-oxazolyl)-6-(trifluoromethyl)

A solution of 13.5 g (0.036 mol) of pyridine,3,5-bis(chlorocarbonyl)-4-cyclobutyl-2-(difluoromethyl)-6-(trifluoromethyl)-in 80 ml of dichloromethane was cooled to 0° C. under a nitrogenatmosphere. To it was added dropwise 9.8 ml of ethanolamine. Aprecipitate formed immediately and the solution became so viscous that70 ml additional dichloromethane was added so that stirring couldcontinue. The reaction mixture was stirred in the cold for 15 minutesthen at room temperature for 3 hours. The reaction solution was pouredinto water and extracted seven times with ethyl acetate. The combinedorganic layers were dried over anhydrous magnesium sulfate, filtered,and concentrated to afford 13.2 g (87%) of white powdery solid of3,5-pyridinedicarboxamide,N,N'-bis(2-hydroxyethyl)-4-cyclobutyl-2-(difluoromethyl)-6-(trifluoromethyl)-.

A 6.0 g (0.014 mol) sample of the above intermediate was refluxed in 100ml of thionyl chloride for 2.5 hours. The thionyl chloride was thenremoved by rotary evaporation. The residue was taken up indichloromethane and washed with water. The organic layer was dried overanhydrous magnesium sulfate to give 2.8 g (42%) of crude product. Twograms of crude product was used directly in a further reaction and 0.8 gwas purified for analysis. The crude product was subjected tochromatography using 50% ethyl acetate in cyclohexane to afford 0.70 g(87% recovery) of 3,5-pyridinedicarboxamide,N,N'-bis(2-chloroethyl)-4-cyclobutyl-2-(difluoromethyl)-6-(trifluoromethyl)-,as a white solid (m.p. 246°-247° C.).

A solution of 2.0 g (0.0043 mol) of this intermediate in 40 ml of dryTHF was cooled to 0° C. under a nitrogen atmosphere. Then was added 1.04g (0.0093 mol) of potassium t-butoxide all at once. The reaction colorimmediately changed from colorless to red and then thirty minutes laterto dark brown. The reaction mixture was stirred in the cold for 30minutes and then at room temperature for 45 minutes. GLC assay shows nostarting material at that time so the solution was poured into NaCl/H₂ Oand extracted with ethyl ether. The organic layer was dried overanhydrous magnesium sulfate, filtered, and concentrated to afford 1.6 g(95%) of crude product. The crude product was chromatographed using 20%ethyl acetate in cyclohexane to yield 0.95 g (56%) of product, as awhite solid (m.p. 186°-187° C.).

    ______________________________________                                        Elemental Analysis:                                                                         C           H      N                                            ______________________________________                                        Calculated    52.45       4.14   10.79                                        Found         52.50       4.18   10.77                                        ______________________________________                                    

EXAMPLE 9

3-pyridinecarbothioic acid,6-(difluoro-methyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-2-(trifluoromethyl)-,S-methyl ester

A solution of 2.5 ml of ethanolamine (0.0394 mole) in 50 ml CH₂ Cl₂ wascooled by an ice bath before adding 7.28 g of 3-pyridinecarbothioicacid,5-(chloro-carbonyl)-6-(difluoromethyl)-4-(2-methylpropyl)-2-(tri-fluoromethyl)-,S-methyl ester (0.0187 mole) in 70 ml CH₂ Cl₂ dropwise. The bath wasremoved and the mixture was stirred magnetically for two hours. Thereaction sat overnight before workup. It was washed with NaCl(aqueous)and extracted with more CH₂ Cl₂. The CH₂ Cl₂ layer was collected, driedwith MgSO₄, filtered and concentrated to an orange oil. This wasdissolved in ethyl acetate and filtered through silica gel. Afterconcentrating, 6.44 g was recovered. 85% yield. A 1.4 g sample waschromatographed in 40% EtOAc/cyclohexane. A pale colored oil (1.16 g)was recovered which gradually solidified. This was recrystallized from10% EtOAc/hexane. There was recovered 0.92 g white crystals: m.p.102°-106° C.

This intermediate (6.15 g=0.0148 mole), 100 ml of xylene and 3.52 g P₂S₅ (0.0157 mole) were combined and refluxed for one hour. A gaschromatographic assay of the xylene phase showed complete reaction. Itwas washed with NaHCO₃ (aqueous) and extracted with ether and ethylacetate. A residue which stuck to the walls of the reaction flask wasalso treated with NaHCO₃ (aqueous) and extracted as above. The organicphases were combined, dried with MgSO₄, filtered and concentrated to adark oil. This was Kugelrohr distilled at 140° C. to give 4.4 g of anorange oil. This was chromatographed in 10% EtOAc/cyclohexane, to give2.7 g of product as a colorless oil which gradually solidified (44%yield) m.p. 97°-99° C.

EXAMPLE 10

3-pyridinecarboxylic acid,6-(difluoro-methyl)-5-(5,6-dihydro-4H-1,3-oxazin-2-yl)-4-(2-methyl-propyl)-2-(trifluoromethyl)-,methyl ester

To 8.4 g (22.5 mmol) of acid chloride starting material used in Example1 in 50 ml of methylene chloride were added 5.4 g of 3-bromopropylaminehydrobromide and 5.5 g of potassium carbonate. The mixture was stirredat room temperature for one hour and then 20 ml of water was added.Stirring was continued for 18 hours. After that the organic layer wasseparated, washed with brine and concentrated. The oily residue wastriturated with cyclohexane to give a solid. A 2.3 g analytically puresample was obtained by chromatography of 2.6 g of crude3-pyridinecarboxylic acid,5-[[(3-bromopropyl)amino]carbonyl]-6-(difluoromethyl)-4-(2-methylpropyl)-2-(trifluoro-methyl)-, methyl ester on silica gelcolumns with 20% ethyl acetate/cyclohexane as eluting solvent, m.p.107°-110° C.

To 2.4 g (5 mmol) of this material in 10 ml of methylene chloridecontaining 0.5 g of benzyltriethylammonium chloride was added in oneportion 10 ml of 50% sodium hydroxide solution and the resultingreaction mixture was stirred at room temperature for 2 hours. Additionalwater and methylene chloride were added and the two layers wereseparated. The organic layer was washed with brine, dried andconcentrated. The oily residue was chromatographed on silica gel (1:5ethyl acetate-cyclohexane) to afford 1.4 g (70%) of product as colorlessoil n_(D) ²⁵ 1.4711.

Anal. Calc'd. for C₁₇ H₁₉ F₅ N₂ O₃ : C, 49.68; H, 5.36; Cl, 25.94; N,3.41 Found: C, 49.78; H, 5.41; Cl, 25.81; N, 3.40

EXAMPLE 11

3-pyridinecarboxylic acid,6-(difluoro-methyl)-5-(5,6-dihydro-4H-1,3-thiazin-2-yl)-4-(2-methylpropyl)-2-(trifluoromethyl)-,methyl ester

A mixture of 5 g (10 mmol) of intermediate of Example 10 and 2.4 g ofphosphorous pentasulfide was 25 heated in 30 ml of xylene at 120°-130°C. for 11/2 hours, then cooled and the xylene solution was decanted. Thegummy precipitate was dissolved in methylene chloride and 2.5N sodiumhydroxide solution. The organic layer was separated, washed with water,brine, dried and concentrated. The crude product was purified by flashchromatography on silica gel (25% ethyl acetate/cyclohexane): yield 0.9g (22%), m.p. 93°-97° C.

Anal. Calc'd. for C₁₇ H₁₉ F₅ N₂ O₂ S₁ : C, 49.76; H, 4.63; N, 6.83; S,7.80 Found: C, 49.64; H, 4.66; N, 6.78; S, 7.88

EXAMPLE 12 3-pyridinecarbothioic acid,6-(difluoro-methyl)-5-(4,5-dihydro-1H-imidazol-2-yl)-4-(2-methyl-propyl)-2-(trifluoromethyl)-,S-methyl ester

To a solution of 3-pyridinecarbothioic acid,5-(chlorocarbonyl)-6-(difluoromethyl)-4-(2-methyl-propyl)-2-(trifluoromethyl)-,S-methyl ester (10 g, 0.0256 mol) in CH₂ Cl₂ (30 mL) was added 5.74 g(0.0282 mol) of 2-aminoethylbromide hydrobromide salt. The mixture wascooled at ice bath and to it was added 9.8 mL (0.056 mol) ofethyldiisopropylamine. The reaction was followed by thin layerchromatograph (silica gel, CH₂ Cl₂). After 20 minutes at 0° C., a majorproduct was formed with no detectable amount of starting material. Themixture was worked up by pouring into water, extracted with CH₂ Cl₂. TheCH₂ Cl₂ layer was washed with water, dried with anhydrous magnesiumsulfate, and concentrated to give 12.2 g of a light brown solid (100%yield). A 10.18 g sample of this solid was purified by liquidchromatograph (10% EtOAc/cyclohexane) to give 7.8 g of3-pyridinecarbothioic acid, 5-[[(2-bromoethyl)amino]carbonyl]-6-(difluoromethyl)-4-(2-methylpropyl)-2-(trifluoromethyl)-,S-methyl ester (76% yield) as a white solid: m.p. 139° C. (softened at123° C. and resolidified at 135° C.).

To a solution of this intermediate (1.5 g, 0.0031 mol) in carbontetrachloride (50 ml) was added 1 g of phosphorus pentachloride. Themixture was refluxed for 1 hour. The reaction gave only one majorproduct as evidenced by ¹ H NMR. The excess reagents were removed byrotary evaporator. To the residual colorless oil was added 30 ml CH₂ Cl₂and the mixture was cooled at ice-bath temperature. To it was addedaqueous ammonia (20 ml). The mixture was stirred at ice bath for 40minutes and then worked up by pouring into water, and extracting withCH₂ Cl₂. The CH₂ Cl₂ layer was washed with water, dried with anhydrousmagnesium sulfate, concentrated to give 1.06 g of a white-foam solid asproduct (86% yield): m.p. 136°-142° C.

EXAMPLE 13 3-pyridinecarbothioic acid,5-(1-amino-4,5-dihydro-1H-imidazol-2-yl)-6-(difluoromethyl)-4-(2-methylpropyl)-2-(trifluoromethyl)-,S-methyl ester

To a solution of the intermediate of Example 12 (1.5 g, 0.0031 mol) incarbon tetrachloride (50 ml) was added 1 g of phosphorus pentachloride.The mixture was refluxed for 1 hour. The reaction gave only one majorproduct as evidenced by ¹ H NMR. The excess reagents were removed byrotary evaporator. To the residual colorless oil was added 30 ml of CH₂Cl₂ and cooled at ice-bath temperature. To it was added 0.6 ml ofhydrazine hydrate (85%) and 1 ml of ethyldiisoproamine. The mixture wasstirred at room temperature overnight and then worked up by pouring intowater and extraction with CH₂ Cl₂. The CH₂ Cl₂ layer was washed withwater, dried with anhydrous magnesium sulfate, concentrated to give 1.15g of a light yellow solid. It was purified by chromatography (50%EtOAc/cyclohexane) to give 0.56 g of product as a light yellow solid(44% yield): m.p. 161°-163° C.

EXAMPLE 14 3-pyridinecarboxylic acid,2-(difluoro-methyl)-5-(3-methyl-2-oxazolidinyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester

A mixture of 2 g (0.00589 mol) of 3-pyridinecarboxylic acid,5-(formyl)-2-(difluoromethyl)-4-(2-methylpropyl)- 6-(trifluoromethyl)-,methyl ester, 1.32 g (0.01768 mol) of N-methylethanolamine, and about0.2 ml water in about 30 ml of toluene with two crystals of p-toluenesulfonic acid as a catalyst was refluxed in a Dean Stark trap for 8hours after which the reaction was complete. The product wasconcentrated in vacuo followed by Kugelrohr distillation (120° at 0.5torr) to give 1.78 g of product as a light yellow oil which solidifiedon standing, m.p. 50°-53° C., yield 76%.

EXAMPLE 15 3-pyridinecarbothioic acid,6-(difluoro-methyl)-5-(5-methyl-1,3,4-oxadiazol-2-yl)-4-(2-methyl-propyl)-2-(trifluoromethyl)-,S-methyl ester

In an oven-dried flask was placed 3.8 g of acetylhydrazide in 30 ml ofdichloromethane (freshly opened bottle). The flask was cooled to 0° C.and to this was added a solution of 10.0 g (0.026 mol) of the startingmaterial of Example 12 in 40 ml of dichloromethane. (All previous stepswere done under a N₂ atmosphere). The acid chloride addition lasted 30minutes, during which time the solution began to turn cloudy. Afteraddition was complete, the solution was stirred at room temperature for3 hours.

During this time a white precipitate was observed. After the 3 hours ofstirring, GLC assay showed no starting material. The reaction solutionwas filtered, collecting the white precipitate. The filtrate was pouredinto H₂ O and extracted with CH₂ Cl₂. The organic layer was washed oncewith water and dried over anhydrous MgSO₄. Concentration gave 4.5 g ofcrude material, which was purified further by chromatography to give 3.2g. Total yield of 3-pyridinecarbothioic acid,5-[(2-acetylhydrazino)carbonyl]-6-(difluoromethyl)-4-(2-methylpropyl)-2-(trifluoromethyl)-, S-methyl ester was 6.7 g, m.p. 186°-187° C.

A mixture of 4.0 g (0.0093 mol) of this intermediate, 7.3 ml ofphosphorus oxychloride, and 2.57 g (0.012 mol) of phosphoruspentachloride was heated at reflux. The mixture became homogeneous andclear. After one hour at reflux, an aliquot of reaction mixture wasremoved and concentrated. The residue was treated with 1-2 ml of icewater and extracted with 2 ml of dichloromethane. TLC in 50% ethylacetate in cyclohexane showed no starting material so the heat wasturned off and the reaction flask was cooled to room temperature. Theflask was placed on a rotary evaporator and the contents were evaporatedto leave an oily residue. The residual oil was treated with ice/H₂ O andextracted with 2×50 ml of dichloromethane and 1×40 ml of ethyl ether.The organics were dried over anhydrous MgSO₄, filtered, and concentratedto afford 4.0 g of crude dark yellow oil. Purification by chromatography(20% ethyl acetate in cyclohexane) afforded 1.5 g (39% yield) of productas a yellow oil.

EXAMPLE 16 3-pyridinecarboxylic acid,2-(difluoro-methyl)-5-(4,5-dihydro-1-methyl-1H-imidazol-2-yl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester

To a 20 g (0.054 mol) solution of the 3-pyridinecarboxylic acid,5-(chlorocarbonyl)-4-(2- methylpropyl)-6-(trifluoromethyl)-, methylester in dichloromethane was added 12.0 g (0.059 mol) of2-bromoethylamine hydrobromide and the solution was cooled in an icebath. Then 10.2 ml (0.059 mol) of N,N-diisopropylethylamine was addeddropwise over 5 minutes. The solution was stirred for 30 minutes andthen the ice bath was removed. Some solid started to form. The solutionwas stirred at room temperature and monitored by TLC (20%EtoAC/cyclohexane) and ¹⁹ F NMR. It was stirred overnight at roomtemperature. In the morning an additional 1.1 equivalent (10.2 ml) ofethyl diisopropylamine was added and let stir. In one hour TLC showed nostarting material. The reaction solution was poured into H₂ O andextracted with CH₂ Cl₂. The organic layer was dried over anhydrousMgSO₄, filtered, and concentrated to yield 24.5 g (99%) of crude lightyellow oil. This was purified by chromatography using (15%EtoAC/cyclohexane) to yield 3-pyridinecarboxylic acid,5-[[(2-bromoethyl)amino]carbonyl]-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester as a white solid: 14 g (57%).

A solution of 2.0 g (0.0043 mol) of this intermediate in 20 ml of CCl₄was refluxed with 1.8 g (0.0086 mol) of phosphorus pentachloride. Thesolution became homogeneous and clear upon heating. One hour later ¹⁹ FNMR showed a new set of peaks. The solution was allowed to stir anadditional hour. ¹ H NMR shows no NH peak at this time. The solventswere evaporated and the flask was placed under vacuum for 3 hours toyield 2.1 g of a white semisolid product. This semisolid product wastaken up in 25 ml of dichloromethane and chilled to 0° C. Then 20 ml ofaqueous methylamine (40%) was added dropwise over 10 minutes. Thesolution was allowed to stir overnight at room temperature. The nextmorning, GLC showed reaction was complete. The reaction solution waspoured into H₂ O and extracted with CH₂ Cl₂. The organics were driedover anhydrous MgSO₄, filtered, and concentrated to give 1.5 g (87%) ofcrude yellow oil. Purification by chromatography using 50% ethyl acetatein cyclohexane yielded 1.1 g (64%) of product as an orange oil.

EXAMPLE 17 3-pyridinecarboxylic acid,2-(difluoro-methyl)-5-(4,5-dihydro-5-methyl-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester

3-pyridinecarboxylic acid,5-(chloro-carbonyl)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester (5.26 g=0.0141 mole), 50 ml CH₂ Cl₂ and 2.5 ml1-amino-2-propanol were combined at room temperature. After 1.5 hours ¹⁹F NMR showed the reaction was complete. The mixture was washed withdilute HCl and extracted with CH₂ Cl₂. The CH₂ Cl₂ layer was dried withMgSO₄, filtered and concentrated to 5.28 g glass. After drying undervacuum, 5.0 g of 3-pyridinecarboxylic acid,2-(difluoromethyl)-5-[[(2-hydroxypropyl)amino]carbonyl]-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester was obtained. Yield was 86%.

This intermediate (4.43 g=0.0107 mole), 50 ml of xylenes and 2.58 g ofP₂ S₅ were refluxed overnight. The organic liquid phase was decantedfrom an oily residue stuck to the walls of the flask. It was washed withNaHCOs(aqueous) and extracted with ether. The ether layer was dried withMgSO₄, filtered and concentrated to 2.9 g of orange oil. A gaschromatographic assay showed it was 99% pure. The residue in thereaction flask was then treated similarly. A dark oil was recoveredwhich was 83% pure by gas chromatographic. This was chromatographed in5% EtOAc/cyclohexane. The best materials were combined and Kugelrohrdistilled at 120° C. to give 2.6 g product as a yellow oil, n_(D) ²⁵1.4935. 60% yield.

EXAMPLE 18 3-pyridinecarboxylic acid,2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester

3-Pyridinecarboxylic acid,2-(difluoromethyl)-5-{[(2-hydroxyethyl)amino]carbonyl}-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester (5.0 g=0.0127 mole), 50 mL xylenes and 1.79 g P₂ S₅ (0.0081mole) were combined and heated at reflux for one hour. A GC assay showedwhat appeared to be starting material and product, so 0.62 g P₂ S₅(0.0028 mole) was added and reflux continued for another three hours. Atthis time, a GC assay showed complete reaction. Heating was stopped andthe reaction mixture sat at room temperature for four days beforeworkup. It was then treated with NaHCO₃ (aqueous) and extracted withether. There was a bad emulsion problem. The ether layer was dried withMgSO₄, filtered, and concentrated to a dark orange oil. This wasKugelrohr distilled to give 3.9 g pale yellow oil which solidified. Thiswas recrystallized from hexanes to give 2.61 g of pale orange crystals(52% yield). mp 79°-81° C.

EXAMPLE 19 3-Pyridinecarboxylic acid,2-(difluoromethyl)-5-(1,3-dithiolan-2-yl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester

A mixture of product of Step 11 (1.78 g=0.0053 mole), 20 mL CH₂ Cl₂, and0.5 mL ethanedithiol were cooled in an ice bath under N₂ before adding0.2 mL TiCl₄. A yellow solid formed. The reaction mixture was warmedslowly to room temperature and was stirred overnight and poured intoNaCl(aqueous) and extracted with CH₂ Cl₂. The CH₂ Cl₂ layer was driedwith MgSO₄, filtered and concentrated to 2.2 g oil. This was Kugelrohrdistilled in fraction to give 1.9 g (86%) of product, n_(D) ²⁵ =1.5180,bp 120° C. (0.1 torr).

EXAMPLE 20 3-Pyridinecarboxylic acid,2-(difluoromethyl)-5-(1,3-dithian-2-yl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester

A mixture of product of Step 11 (1.7 G=0.005 mole), 20 mL CH₂ Cl₂ and0.6 mL 1,3-propanedithiol were cooled in an ice bath before adding 0.3mL TiCl₄. A solid formed immediately. After 15 minutes the bath wasremoved. One hour later a GC assay showed complete reaction. It waswashed with NaCl (aqueous) and extracted with CH₂ Cl₂. The CH₂ Cl₂ layerwas dried with MgSO₄, filtered and concentrated to a colorless oil. Thiswas Kugelrohr distilled at 130° C. to give 1.95 g of product as an oilwhich gradually solidified. 91% yield; mp 72°-76° C.

EXAMPLE 21 3-Pyridinecarboxylic acid,5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-2,6-bis(trifluoromethyl)-,methyl ester

A mixture of 10.1 g (˜0.025 mol) of2,6-bis(trifluoromethyl)-4-(2-methylpropyl)-3,5-pyridinedicarboxylicacid and its monomethyl ester, prepared from partial hydrolysis ofdimethyl2,6-bis(trifluoro-methyl)-4-(2-methylpropyl)-3,5-pyridinedicarboxylate,10 mL (0.11 mol) oxalyl chloride, 2 drops DMF, and 75 mL chloroform isstirred at room temperature for 18 hours and stripped. The residue isdissolved in 200 mL CH₂ Cl₂ /100 mL THF and 7 g (0.10 mol) ethanolamineadded. The mixture is stirred at ambient temperature for 1 hour andstripped. From work-up with aqueous HCl/ethyl acetate, 8.5 gintermediate is obtained. The intermediate is heated to reflux with 17 g(0.038 mol) phosphorus pentasulfide in 250 mL xylene and held at refluxfor 18 hours. Work-up with ether/sodium bicarbonate solution andpurification/separation by HPLC (10% ethyl acetate) gives 2.87 g (˜50%yield) orange brown solid, mp 92°-5°.

EXAMPLE 22 Pyridine,3,5-bis(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-2,6-bis(trifluoromethyl)

A second product isolated by HPLC as described in Example 21 isKugelrohr distilled to give 0.55 g (˜10%) tan solid, mp 143°-146° C.

EXAMPLE 23 3-Pyridinecarboxylic acid,2-(chlorodi-fluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methyl-propyl)-6-(trifluoromethyl)-,methyl ester

To a solution of 0.0082 mol lithium diisopropylamide in 30 mL THF atbelow -65° C. is added a solution of 3.0 g (0.0076 mol) of product ofExample 18 in 15 mL THF. The mixture is held at below -65° C. for 20minutes and 2.2 g (0.009) hexachloroethane in 10 mL THF is added. Themixture is allowed to warm to room temperature. Work-up with CH₂ Cl₂/dilute HCl and Kugelrohr distillation at 150-160/1.2 gives crudeproduct which is purified using a chromatrograph (5% ethyl acetate) andrecrystallization from hexane to give 0.20 g (6% yield) white solid, mp114°-6° C.

EXAMPLE 24 3-Pyridinecarboxylic acid,4-[bis(methylthio)methyl]-6-(difluoromethyl)-5-(4,5-dihydro-2-oxazolyl)-2-(trifluoromethyl)-,methyl ester

To a solution of 3.8 g (0.0098 mol) of 3-pyridinecarboxylic acid,6-(difluoromethyl)-5-(4,5-dihydro-2-oxazolyl)-4-[(methylthio)methyl]-2-(trifluoromethyl)-,methyl ester in 50 mL anhydrous THF in a dry flask under nitrogen isadded 40 mL (0.04 mol) 1.0 m lithium bis(trimethylsilyl)amide in hexane,controlling the reaction temperature at -20° to -10° C. After 10 minutesat -10° C., 1.9 mL (0.014 mol) methyl disulfide is added. The reactionmixture is warmed to 20° C., where it is stirred for 3 hours. Thereaction mixture is worked up using dilute HCl and ether. The product ispurified by HPLC (20% ethylacetate in cyclohexane) and Kugelrohrdistilled to give 1.03 g (24% yield) yellow-brown oil, n_(D) ²⁵ =1.5235,bp 180°-190° C./1.4 torr.

EXAMPLE 25 3-Pyridinecrboxylic acid,2-(difluoro-methyl)-4-(2-methylpropyl)-5-[3-(trifluoroacetyl)-2-thiazolidinyl]-6-(trifluoromethyl)-,methyl ester

A mixture of 6.0 g (0.015 mol) of product of Example 18, 6 mL (0.042mol) trifluoroacetic anhydride, 30 g (0.26 mol) trifluoroacetic acid, 18g (0.27 mol) zinc dust and 150 mL methylene chloride is heated and heldat reflux for 2 hours. Another 1 g zinc dust is added and the mixtureheld at reflux for 1 hour. The mixture is cooled and filtered, and thefiltrate concentrated. Purifiction by chromatography (40% methylenechloride in cyclohexane) affords 1.88 g (25% yield) of a first fractionas a yellow-green oil.

EXAMPLE 26 3-Pyridinecarboxylic acid,2-methyl-4-(2-methylpropyl)-5-[3-(trifluoroacetyl)-2-thiazolidinyl]-6-(trifluoromethyl),methyl ester

Flushing the HPLC column from Example 25 with methylene chloride elutesthe crude product which after chromotography (7% ethyl acetate incyclohexane) and Kugelrohr distillation yields 0.54 g (7% yield) yellowoil, bp 185°-195° C./1.0 torr.

Further compounds according to this invention were prepared by methodssimilar to those described above and are shown in the following Table 1along with a physical property for each where available.

                                      TABLE 1                                     __________________________________________________________________________    Example                                                                       No.  Compound                M.P./B.P.                                                                              n.sub.D .sup.25                         __________________________________________________________________________    27   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        87.0-89.0                                             5-(4,5-dihydro-2-oxazolyl)-4-(2-methylpropyl)-                                2-(trifluoromethyl)-, methyl ester                                       28   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                        85.0-87.0                                             5-(4,5-dihydro-2-oxazolyl)-4-(2-methylpropyl)-                                6-(trifluoromethyl)-, methyl ester                                       29   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        81.0-83.0                                             5-(4,5-dihydro-2-oxazolyl)-4-(1-methylethyl)-                                 2-(trifluoromethyl)-, methyl ester                                       30   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        101.0-103.0                                           5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-                               2-(trifluoromethyl)-, methyl ester                                       31   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                        67.0-68.0                                             5-(4,5-dihydro-2-oxazolyl)-4-(1-methylethyl)-                                 6-(trifluoromethyl)-, methyl ester                                       32   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                        40.0-41.0                                             5-(4,5-dihydro-2-oxazolyl)-4-propyl-6-(tri-                                   fluoromethyl)-, methyl ester                                             33   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                        80.0-82.0                                             5-(5-methoxy-2-oxazolyl)-4-(2-methylpropyl)-                                  6-(trifluoromethyl)-, methyl ester                                       34   3-pyridinecarboxylic acid, 4-(cyclopropylmethyl)-                                                              1.5090                                       2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-                               6-(trifluoromethyl)-, methyl ester                                       35   3-pyridinecarboxylic acid, 4-(cyclopropylmethyl)-                                                     63.0-65.0                                             2-(difluoromethyl)-5-(4,5-dihydro-2-oxazolyl)-                                6-(trifluoromethyl)-, methyl ester                                       36   3-pyridinecarbothioic acid, 2-(difluoromethyl)-                                                       74.0-76.0                                             5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-                               6-(trifluoromethyl)-, S-methyl ester                                     37   3-pyridinecarboxylic acid, 4-cyclobutyl-2-                                                            88.0-89.0                                             (difluoromethyl)-5-(4,5-dihydro-2-oxazolyl)-                                  6-(trifluoromethyl)-, methyl ester                                       38   3-pyridinecarboxylic acid, 4-cyclobutyl-2-                                                            75.0-77.0                                             (difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-                                 6-(trifluoromethyl)-, methyl ester                                       39   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                        125.0 @                                               5-(4,5-dihydro-2-thiazolyl)-4-(1-methylethyl)-                                                        0.400 torr                                            6-(trifluoromethyl)-, methyl ester                                       40   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                        125.0 @                                               5-(4,5-dihydro-2-thiazolyl)-4-propyl-6-(tri-                                                          0.250 torr                                            fluoromethyl)-, methyl ester                                             41   3-pyridinecarbothioic acid, 2-(difluoromethyl)-                                                       95.0-97.0                                             5-(4,5-dihydro-2-oxazolyl)-4-(2-methylpropyl-                                 6-(trifluoromethyl)-, S-methyl ester                                     42   3-pyridinecarbothioic acid, 4-(cyclopropylmethyl)-                                                    91.0-95.0                                             2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-                               6-(trifluoromethyl)-, S-methyl ester                                     43   3-pyridinecarbothioic acid, 4-(cyclopropylmethyl)-                                                    67.0-72.0                                             2-(difluoromethyl)-5-(4,5-dihydro-2-oxazolyl)-                                6-(trifluoromethyl)-, S-methyl ester                                     44   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                        57.0-60.0                                             4-(2-methylpropyl)-5-(2-thiazolyl)-6-(tri-                                    fluoromethyl)-, methyl ester                                             45   3-pyridinecarbothioic acid, 4-(cyclopropyl-                                                           127.0-130.0                                           methyl)-6-(difluoromethyl)-5-(4,5-dihydro-                                    2-thiazolyl)-2-(trifluoromethyl), S-methyl ester                         46   3-pyridinecarbothioic acid, 4-(cyclopropyl-                                                           109.0-113.0                                           methyl)-6-(difluoromethyl)-5-(4,5-dihydro-2-                                  oxazolyl)-2-(trifluoromethyl)-, S-methyl ester                           47   pyridine,2-(difluoromethyl)-5-(4,5-dihydro-2-                                                          99.0-102.0                                           thiazolyl)-4-(2-methylpropyl)-3-(1H-pyrazol-                                  1-ylcarbonyl)-6-(trifluoromethyl)-                                       48   3-pyridinecarbothioic acid, 4-cyclobutyl-6-                                                           118.0-119.0                                           (difluoromethyl)-5-(4,5-dihydro-2-oxazolyl)-                                  2-(trifluoromethyl)-, S-methyl ester                                     49   3-pyridinecarboxylic acid, 4-cyclobutyl-6-                                                            112.0-113.0                                           (difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-                                 2-(trifluoromethyl)-, methyl ester                                       50   3-pyridinecarbothioic acid, 4-cyclobutyl-6-                                                           138.0-139.0                                           (difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-                                 2-(trifluoromethyl)-, S-methyl ester                                     51   3-pyridinecarboxylic acid, 4-cyclobutyl-6-                                                            105.0-107.0                                           (difluoromethyl)-5-(4,5-dihydro-2-oxazolyl)-                                  2-(trifluoromethyl)-, methyl ester                                       52   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                        80.0-83.0                                             5-(5-methyl-1,3,4-oxadiazol-2-yl)-4-(2-                                       methylpropyl)-6-(trifluoromethyl)-, methyl ester                         53   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        128.0-130.0                                           5-(4,5-dihydro-2-thiazolyl)-4-methyl-2-(tri-                                  fluoromethyl)-, methyl ester                                             54   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        118.0-120.0 (m.p.)                                    5-(4,5-dihydro-2-oxazolyl)-4-methyl-2-(tri-                                                           125.0-136.0 (b.p.)                                    fluoromethyl)-, methyl ester                                                                          @ 1.300 torr                                     55   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        102.0-104.0                                           5-(4,5-dihydro-2-oxazolyl)-4-[(methylthio)                                    methyl]-2-(trifluoromethyl)-, methyl ester                               56   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        88.0-90.0 (m.p.)                                      5-(4,5-dihydro-2-thiazolyl)-4-[(methylthio)                                                           175.0-185.0 (b.p.)                                    methyl]-2-(trifluoromethyl)-, methyl ester                                                            @ 1.200 torr                                     57   3-pyridinecarbothioic acid, 6-(difluoromethyl)-                                                                1.5009                                       5-(5,6-dihydro-4H-1,3-oxazin-2-yl)-4-(2-                                      methylpropyl)-2-(trifluoromethyl)-, S-methyl                                  ester                                                                    58   3-pyridinecarbothioic acid, 6-(difluoromethyl)-                                                       71.0-75.0                                             5-(5,6-dihydro-4H-1,3-thiazin-2-yl)-4-(2-                                     methylpropyl)-2-(trifluoromethyl)-, S-methyl                                  ester                                                                    59   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                                 1.5008                                       5-(5,6-dihydro-4H-1,3-thiazin-2-yl)-4-(2-                                     methylpropyl)-6-(trifluoromethyl)-, methyl                                    ester                                                                    60   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                                 1.4706                                       5-(5,6-dihydro-4H-1,3-oxazin-2-yl)-4-(2-                                      methylpropyl)-6-(trifluoromethyl)-, methyl                                    ester                                                                    61   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                        190.0-220.0                                           5-(5,6-dihydro-4H-1,3-oxazin-2-yl)-4-(2-                                      methylpropyl)-6-(trifluoromethyl)-                                       62   3-pyridinecarbothioic acid, 2-(difluoromethyl)-                                                       60.0-65.0                                             5-(5,6-dihydro-4H-1,3-oxazin-2-yl)-4-(2-                                      methylpropyl)-6-(trifluoromethyl)-, S-methyl                                  ester                                                                    63   Pyridine, 3,5-bis(5,6-dihydro-4H-1,3-oxazin-                                                          108.0-115.0                                           2-yl)-2-(difluoromethyl)-4-(2-methylpropyl)-                                  6-(trifluoromethyl)                                                      64   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                          110 @ 0.100                                         5-(4,5-dihydro-5-methyl-2-oxazolyl)-4-(2-                                                             torr                                                  methylpropyl)-6-trifluoromethyl)-, methyl                                     ester                                                                    65   3-pyridinecarbothioic acid, 2-(difluoromethyl)-                                                       87.0                                                  5-(4,5-dihydro-5-methyl-2-thiazolyl)-4-(2-                                    methylpropyl)-6-(trifluoromethyl)-, S-methyl                                  ester                                                                    66   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                          100 @ 0.100                                         5-(4,5-dihydro-4-methyl-2-thiazolyl)-4-(2-                                                            torr                                                  methylpropyl)-6-(trifluoromethyl)-, methyl                                    ester                                                                    67   3-pyridinecarboxylic acid, 5-(4,5-dihydro-                                                            81.0-83.0 (m.p.)                                      2-thiazolyl)-6-methyl-4-(2-methylpropyl)-                                                             155.0-165.0 (b.p.)                                    2-(trifluoromethyl)-, methyl ester                                                                    @ 1.200 torr                                     68   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        77.0-79.0 (m.p.)                                      5-(5,6-dihydro-4H-1,3-thiazin-2-yl)-4-                                                                175.0-185.0 (b.p.)                                    [(methylthio)methyl]-2-(trifluoromethyl)-,                                                            @ 1.200 torr                                          ethyl ester                                                              69   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        170.0-180.0                                           5-(5,6-dihydro-4H-1,3-oxazin-2-yl)-4-[(methyl-                                                        @ 1.200 torr                                          thio)methyl]-2-(trifluoromethyl)-, ethyl                                      ester                                                                    70   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                                 1.4675                                       5-(5,6-dihydro-6-methyl-4H-1,3-oxazin-2-yl)-                                  4-(2-methylpropyl)-6-(trifluoromethyl)-,                                      methyl ester                                                             71   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                                 1.4684                                       5-(5,6-dihydro-6-methyl-4H-1,3-oxazin-2-yl)-                                  4-(2-methylpropyl)-6-(trifluoromethyl)-, methyl                               ester                                                                    72   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                          110 @ 0.100                                         5-(4,5-dihydro-4-methyl-2-oxazolyl)-4-(2-                                                             torr                                                  methylpropyl)-6-(trifluoromethyl)-, methyl                                    ester                                                                    73   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                          120 @ 0.100                                         5-(4-ethylidene-4,5-dihydro-5-oxo-2-oxazolyl)-                                                        torr                                                  4-(2-methylpropyl)-2-(trifluoromethyl)-,                                      methyl ester                                                             74   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                          130 @ 0.100                                         5-(4-ethylidene-4,5-dihydro-5-oxo-2-oxazolyl)-                                                        torr                                                  4-(2-methylpropyl)-6-(trifluoromethyl)-,                                      methyl ester                                                             75   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        143.0-146.0                                           5-[4,5-dihydro-5-methyl-5-(1-methylethyl)-4-                                  oxo-1H-imidazol-2-yl]-4-methyl-2-(trifluoro-                                  methyl)-, methyl ester                                                   76   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                5-[4,5-dihydro-5-methyl-5-(1-methylethyl)-4-                                  oxo-1H-imidazol-2-yl]-4-methyl-6-(trifluoro-                                  methyl)-, methyl ester                                                   77   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        145.0-149.0                                           5-(1,3-dithiolan-2-yl)-4-(2-methylpropyl)-2-                                  (trifluoromethyl)-, methyl ester                                         78   3-pyridinecarboxylic acid, 2-(difluoromethyl)-                                                        120.0-0.0                                             4-(2-methylpropyl)-5-(1,3,4-oxadiazol-2-yl)-                                                          @ 0.250 torr                                          6-(trifluoromethyl)-, methyl ester                                       79   3-pyridinecarboxylic acid, 6-(difluoromethyl)-                                                        115.0-118.0                                           5-(1,3-dithian-2-yl)-4-(2-methylpropyl)-2-                                    (trifluoromethyl)-, methyl ester                                         80   3-pyridinecarboxylic acid, 4-(cyclopropyl-                                                            135.0-0.0                                             methyl)-2-(difluoromethyl)-5-(5-methyl-1,3,4-                                                         @ 0.300 torr                                          oxadiazol-2-yl)-6-(trifluoromethyl)-, methyl                                  ester                                                                    81   3-pyridinecarboxylic acid, 4-(cyclopropyl-                                                            135.0-0.0                                             methyl)-2-(difluoromethyl)-5-(5-methyl-1,3,4-                                                         @ 0.300 torr                                          oxadiazol-2-yl)-6-(trifluoromethyl)-, methyl                                  ester                                                                    82   3-pyridinecarboxylic acid, 4-(cyclopropyl-                                                              115 @ 0.100                                         methyl)-2-(difluoromethyl)-5-(4,5-dihydro-                                                            torr                                                  4-methyl-2-thiazolyl)-6-(trifluoromethyl)-,                                   methyl ester                                                             83   3-pyridinecarboxylic acid, 5-(4,5-dihydro-4-                                                            125 @ 0.100                                         methyl-1,3,4-oxadiazol-2-yl)-2-(difluoromethyl)-                                                      torr                                                  4-(2-methylpropyl)-6-(trifluoromethyl)-,                                      methyl ester                                                             __________________________________________________________________________

EXAMPLE 84 3-Pyridinecarbodithioic acid,2-(difluoro-methyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methyl-propyl)-6-(trifluoromethyl)-,methyl ester

A mixture of 5.0 g (0.01261 mole) of 3-pyridinecarboxylic acid,2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoro-methyl)-,methyl ester and 6.1 g (0.01513 mol) of Lawesson's reagent in 45 mL ofxylenes and 11 mL of HMPA was refluxed under nitrogen for five hours.Reaction was allowed to cool to room temperature and was then passedthrough a plug of silica gel (eluted with ethyl acetate:hexanes=1:5).The resulting material was purified by chromatography (ethylacetate:hexanes=1:10). The resulting orange oil crystallized onstanding. Crystals were washed with hexanes to give 1.26 g (23%) of thetitle compound as orange crystals (MP 102°-106° C.). Anal. Calcd for C₁₆H₁₇ F₅ N₂ S₃ : C, 44.85; H, 4.00; N, 6.54. Found: C,44.96; H,4.01;N,6.53.

EXAMPLE 85 3-Pyridinecarboxamide,2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl-N-methyl-4-(2-methyl-propyl)-6-(trifluoromethyl)-

A mixture of 12.5 g (0.031 mole) of 3-pyridinecarbonyl chloride,2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl-4-(2-methylpropyl)-6-(trifluoro-methyl-;20 mL of a 40% aqueous methylamine solution, 80 mL of water, and 200 mLof methylene chloride were stirred together at room temperature for fourhours. The layers were separated and the organic phase was dried overanhydrous magnesium sulfate. Concentration in vacuo gave a crystallinematerial that was recrystallize ethylene chloridehexanes. Obtained 10.71g (86%) of the title compound as fine white flakes (MP 203°-205° C.).Anal. Calc'd for C₁₆ H₁₈ F₅ N₃₀ Sl: C, 48.60; H, 4.59; N, 10.63. Found:C, 48.51; H, 4.61; N, 10.61.

EXAMPLE 86 3-Pyridinecarbonitrile, 2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-N-methyl-4-(2-methylpropyl)-6-(trifluoromethyl)-

A mixture of 7.0 g (0.01835 mole) of 3-pyridinecarboxyamide,2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoro-methyl)-;and 40 mL of phosphorus oxychloride were refluxed overnight undernitrogen. The mixture was concentrated in vacuo to give a residue thatwas taken up in ethyl acetate and washed with a sodium bicarbonatesolution. Dried over anhydrous magnesium sulfate and concentrated invacuo to give a crystalline product. The product was passed through aplug of silica gel (ethyl acetate:hexanes=1:1) followed byrecrystallization from methylene chloride-hexanes. Obtained 5.14 g (77%)of the title compound as colorless prisms (MP 106°-107° C.). Anal.Calc'd for C₁₅ H₁₄ F₅ N₃ S₁ : C,49.59; H,3.88; N,11.61. Found: C,49.65;H,3.90; N,11.56.

EXAMPLE 87 3-Pyridinecarboximidothioic acid,2-(difluoro-methyl)-5-(4,5-dihydro-2-thiazolyl)-N-methyl-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester

3-Pyridinecarboxamide, 2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-N-methyl-4-(2-methylpropyl)-6-(trifluoromethyl)- (3.78 g, 0.00956 mole)and 2.0 g (0.00956 mole) of phosphorous pentachloride were refluxedtogether in 40 mL of carbon tetrachloride under nitrogen for 15 hours.The reaction mixture was concentrated in vacuo and the resulting oil wastaken up in 30 mL of anhydrous dimethylformamide. This solution wastreated with 1.0 g (0.01434 mole) of sodium methanethiolate, and wasstirred for three hours under nitrogen. The reaction was poured into 150mL of water followed by extraction with ether. The ether extracts werewashed with water then dried over anhydrous magnesium sulfate. Silicagel chromatography (ethyl acetate:hexanes=1:2) gave an oil that wasKugelrohr distilled (160° C.,0.2 mm) to give 1.33 g (33%) of the titlecompound as a thick yellow oil. Anal. Calc'd for C₁₇ H₂₀ F₅ N₃ S₂ :C,47.99; H,4.74; N,9.88. Found: C,47.89; H,4.77; N,9.84.

EXAMPLE 88 3-Pyridinecarboxylic acid, 2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methyl-propyl)-6-(trifluoromethyl)-,cyanomethyl ester

A 3.5 g(0.009 mole) sample of 3-pyridinecarboxylic acid,2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,in 65 mL of DMF was stirred with 1.37 g (0.018 mole) ofchloroacetonitrile and 2.5 g(0.018 mole) of potassium carbonate at RTfor 12 hours. The reaction mixture was poured into dichloromethane andwater was added. The layers were separated and the organics were driedover MgSO₄. Filtration, concentration, and Kugelrohr distillation gave2.1 g (55%) of product, which solidified upon standing (m.p. 146°-147°C.). Anal. Calc'd for C₁₇ H₁₆ F₅ N₃ O₂ S₁ : C,48.45; H,3.83; N,9.97.Found: C,48.43; H,3.82; N,9.96.

EXAMPLE 89 3-Pyridinecarboxylic acid, 6-(difluoromethyl)-4-(2-methylpropyl)-5-(1-methyl-1H-tetrazol-5-yl)-2-(trifluoromethyl)-, methylester

A solution of 5 mL of aqueous methylamine in 15 mL of CH₂ Cl₂ was cooledto 5° C. Then was added 3.0 g of 3-pyridinecarboxylic acid,5-(carbonylchloride)-6-(difluoromethyl)-4-(2-methylpropyl)-2-(trifluoromethyl)-,methyl ester in 20 mL of CH₂ Cl₂. The ice bath was removed and the GLCone hour later shows no starting material. The reaction solution waspoured into water and extracted with CH₂ Cl₂. The organics were dried,filtered, and concentrated to give 2.72 g of the amide. The methylamidewas taken up in 35 mL of CCl₄ and refluxed with 1.5 g of phosphoruspentachloride for 3 hours. ¹⁹ FNMR shows reaction complete. The solutionwas concentrated to dryness and dried under high vacuum for 4 hours togive 2.6 g of a yellow oil, the iminoyl chloride. The 2.6 g (0.0067mole) sample of the iminoyl chloride was taken up in DMF and placed inan addition funnel. A 100 mL rb flask was charged with 0.82 g (0.012mol) of sodium azide in 15 mL of DMF and the solution was cooled to 5°C. with an ice bath. The iminoyl chloride solution was then addeddropwise to the suspension of sodium azide over 30 minutes. The ice bathwas removed and the solution stirred for 25 minutes. The reactionmixture was allowed to sit overnight at RT. Then approximately 4 mL ofwater was added, just enough to produce a cloudiness, and the flask wascooled in an ice bath. The crystals that formed were collected, washedwith ethanol/water followed by a wash with water. Drying gave 1.28 g(49%) of the title compound, as white crystals (m.p. 110.0°-111.0° C.).Anal. Calc'd for C₁₅ H₁₆ F₅ N₅ O₂ : C,45.81; H,4.10; N,17.80. Found:C,46.22; H,4.13; N,17.92.

EXAMPLE 90 3-Pyridinecarboxylic acid,6-(difluoromethyl)-5-(4,5-dihydro-5-oxo-1,3,4-oxadiazol-2-yl)-(2-methylpropyl)-2-(trifluoromethyl)-,methyl ester

A solution of 10.0 g (0.027 mole) of 3,5-pyridinedicarboxylic acid,2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-, 3-hydrazide5-methyl ester in 180 mL of chlorobenzene was brought to reflux.Phosgene was bubbled into the reaction mixture for one hour while thereaction was monitored by GLC. The mixture was allowed cool and then wasconcentrated in vacuo to give an oil which crystallized on standing.Recrystallized product from methylene chloride-hexanes to give 6.5 g(60%) of the title compound as a white solid (MP 106°-108° C.). Anal.Calc'd for C₁₅ H₁₄ F₅ N₃ O₄ : C,45.57; H,3.58; N,10.63. Found: C,45.66;H,3.62; N,10.63.

EXAMPLE 91 3-Pyridinecarboxylic acid,2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,2-propenyl ester

A solution of 2.0 g (0.005 mole) of 3pyridinecarbonyl chloride,2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,in 40 mL of toluene and 0.67 mL (0.01 mole) of allyl alcohol was heatedat reflux overnight. The solution was then cooled, then poured intowater, and extracted with ethyl ether. The organics were dried overMgSO₄, filtered, and concentrated to give 1.2 g of crude product.Purification on the chromatotron using 15% ethyl acetate in cyclohexaneafforded 0.85 g (40%) of the title compound, as an oil (b.p. 135° C.;0.2mm n_(D) ²⁵ 1.5693). Anal. Calc'd for C₁₈ H₁₉ F₅ N₂ O₂ S₁ : C,51.18;H,4.53; N,6.63. Found: C,51.36; H,4.56; N,6.62.

EXAMPLE 92 3-Pyridinecarboxylic acid, 2-(difluoro-methyl)-4-(2-methylpropyl)-5-(5-oxazolyl)-6-(tri-fluoromethyl)- methyl ester

A mixture of 3.4 g (0.10 mole) of 3-pyridinecarboxylic acid,2-(difluoromethyl)-4-(2-methylpropyl)-formyl-6-(trifluoromethyl)-,methyl ester, 1.95 g (0.10 mole) of tosylmethyl isocyanide, and 1.4 g(0.10 mole) of potassium carbonate in 50 mL of methanol was refluxed forthree hours under nitrogen. Concentrated reaction mixture in vacuo andtook residue up into ethyl acetate followed by washing with water thenwith brine. Dried over anhydrous magnesium sulfate and concentrated invacuo to give and oil which was purified by silica gel chromatography(ethyl acetate:hexanes =1:4). Resulting oil was Kugelrohr distilled(120° C., 0.4 mm) to give 2.4 g (63%) of the title compound (n_(D) ²⁵=1.4754). Anal. Calcd for C₁₆ H₁₅ F₅ N₂ O₃ : C,50.80; H,4.00; N,7.41.Found: C,50.70; H,4.04; N,7.33.

EXAMPLE 93 3-Pyridinecarboxylic acid,6-(difluoromethyl)-5-(1,3-dioxan-2-yl)-4-(2-methylpropyl)-2-(tri-fluoromethyl)-,methyl ester

A mixture of 2.0 g (0.0059 mole) of 3-pyridinecarboxylic acid,6-(difluoromethyl)-4-(2-methylpropyl)-5-formyl-2-(trifluoromethyl)-,methyl ester, 2.6 g (0.0118 mol) of 1,3-(bistrimethylsilyloxy)propane,and 20 mg. of trimethylsilyl trifluoromethanesulfonate were stirredunder nitrogen for two hours. Reaction was quenched by the addition of0.2 mL of pyridine. The resulting mixture was passed through a plug ofsilica gel (ethyl acetate:hexanes=1:5) to remove excess reagents. Theresulting oil was purified by silica gel chromatography on achromatotron (ethyl acetate:hexanes=1:5) to give a colorless oil whichwas Kugelrohr distilled (140° C. @0.15 mm) to give 1.00 g (43%) of thetitle compound which crystallized on standing (MP 79°-81° C.). Anal.Calc'd for C₁₇ H₂₀ F₅ N₁ O₄ : C,51.39; H,5.07; N,3.53. Found:C,51.31;.H,5.09; N,3.51.

EXAMPLE 94 3-Pyridinecarboxylic acid, 2-(difluoromethyl)-4-(2-methylpropyl)- 5-(1,3-oxathiolan-2-yl)-6-(trifluoromethyl)-, methylester

A flame dried flask was charged with 2.0 g (0.0059 mol) of3-pyridinecarboxylic acid,2-(difluoromethyl)-5-formyl-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester, 15 mL of dichloromethane, and 0.55 g (0.0071 mol) of2-mercaptoethanol and placed in an ice/methanol bath. Added 0.15 mL oftitanium tetrachloride and the solution was stirred at low temperaturefor for 30 minutes then at RT overnight. The solution was poured intowater and extracted with ethyl ether. The organics were dried overMgSO₄, filtered, and concentrated to give 2.3 g of crude oil. Kugelrohrdistillation afforded 0.55 g (23%) of the title compound, as a clearcolorless oil (b.p.132° C.;0.40 mm, n_(D) ²⁵ 1.4915). Anal. Calc'd forC₁₆ H₁₈ F₅ N₁ O₃ S₁ C,48.12; H,4.54; N,3.50. Found: C,48.14; H,4.57;N,3.49.

EXAMPLE 95 3-Pyridinecarboxylic acid,2-(difluoromethyl)-5-(1,3-dioxolan-2-yl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester

To a stirred anhydrous dichloromethane solution (1.5 mL) containing 19.5mg of trimethylsilyl trifluoromethanesulfonate was added 4.3 mL (0.018mol) of 1,2- bis(trimethylsiloxyethane) and 3.0 g (0.0088 mol) of3-pyridinecarboxylic acid,2-(difluoromethyl)-5-formyl-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester at -78° C. The solution was stirred at -78° C. for 15minutes, then at -20° C. for 30 minutes, and finally the reaction wasstirred at 5° C. for 2 hours. Added 0.3 mL of anhydrous pyridine. Thesolution was poured into saturated NaHCO₃ and extracted with ethylether. The ether extracts were dried over a combination of sodiumcarbonate and sodium sulfate. Filtration, concentration, andpurification using a chromatograph (7:1 hexanes to ethyl acetate)afforded 0.89 g (26%) of the title compound, as a white solid (m.p.56°-57° C.). Anal. Calc'd for C₁₆ H₁₈ F₅ N₁ O₄ : C,50.13; H,4.73;N,3.65. Found: C.50.21; H,4.83; N,3.59.

EXAMPLE 96 3-Pyridinecarboxylic acid,2-(dichloromethyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester

3-Pyridinecarboxylic acid,2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-,methyl ester (5.38 g, 0.0136 mol), 60 mL of methylene chloride and 6.39g of aluminum chloride were combined under a nitrogen atmosphere at 10°C. After five minutes the ice bath was removed, and the reaction wasallowed to warm to room temperature. The reaction gradually darkened incolor over 30 minutes after which time ¹⁹ FNMR indicated completion. Themixture was poured into ice/water followed by extraction with methylenechloride. The extracts were dried over anhydrous magnesium sulfate andconcentrated in vacuo. The residue was purified by silica gelchromatography (methylene chloride/cyclohexane=1:1) followed byrecrystallization from hexanes. The-pure product was combined withproduct from a previous experiment to give 4.1 g (48%) of the titlecompound as a white solid (MP 119°-120° C.).

EXAMPLE 97 3-Pyridinecarboxylic Acid,2-(chlorodifluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-6-(1-methylethyl)-4-(2-methylpropyl)-,Methyl Ester

Through a solution of 240 g of t-butyl isobutyrylacetate in 500 ml ofmethanol was passed 70 g of ammonia in 2 hours, maintaining thetemperature at below 25° C. The resulting solution was stirred at roomtemperature for 18 hours, after which the methanol was removed in vacuo.Methylene chloride was added and the suspension was filtered. Thefiltrate was concentrated on a rotary evaporator to give 180 g t-butyl3-amino-4-methyl-2-pentenoate as an oil.

A solution of 18.6 g (0.1 mol) of methyl chlorodifluoroacetoacetate, 8.4g (0.1 mol) of isovaleraldehyde and 20.5 g (0.1 mol) of t-butyl3-amino4-methyl-2-penenoate in 80 ml of THF containing 1 ml ofpiperidine was refluxed for 18 hours. Then the solution was concentratedin vacuo to give 46 g of crude tetrahydropyridine as an oil.

To a solution of 27 g of the crude tetrahydropyridine and 20 ml of DBUin 80 ml of methylene chloride was added dropwise 9 ml oftrifluoroacetic anhydride at below 12° C. and the resulting solution wasstirred at room temperature for 18 hours. Water was added and the twolayers were separated. The organic layer was washed with 2N HCl, waterand brine, then dried and concentrated to give 22 g of crudedihydropyridine as an oil.

To a solution of 22 g of the crude dihydropyridine in 120 ml ofmethylene chloride was added in portions 12 g of2,3-dichloro-5,6-dicyano-1,4-benzoquinone keeping the reactiontemperature at 20°-30° C. and then stirred at room temperature for 3hours, after which the suspension was filtered and the cake was washedthoroughly with methylene chloride. The filtrate was washed withsaturated sodium bicarbonate solution and the brine then dried andconcentrated. Column chromatography on silica gel (2%ethylacetatecyclohexane) gave 7.8 g of crude pyridinedicarboxylate as anoil.

To a solution of acid chloride (prepared from 11 g ofpyridinedicarboxylate) in 50 ml of CH₂ Cl₂ was added dropwise a solutionof 7 g of 2-aminoethanol in 50 ml CH₂ Cl₂ at below 10° C. and thesolution was then sitrred at room temperature for 18 hours. 2N HCl wasadded and the organic layer was separated, washed with H₂ O, brine,dried and concentrated. Column chromatography on silica gel (35%ethylacetatecyclohexane) gave 4.4 g of 3-pyridinecarboxylic acid,2-(chlorodifluoromethyl)-5-([[(2-hydroxyethyl)aminocarbonyl]-6-(1-methylethyl)-4-(2-methylpropyl)-, methyl ester as a whitesolid. m.p. 114°-120° C.

A mixture of 4 g (10 mmol) of N-(2-hydroxyethyl) amide and 2.2 g ofphosphorus pentasulfide in 100 ml of xylene was heated under reflux for18 hours. Ether and saturated sodium bicarbonate solution were added.The organic layer was separated, washed with water, and then brine,dried and concentrated. Column chromatography on silica gel (6%ethylacetatecyclohexane) gave 1.4 g (32%) of brownish colored solid.m.p. 107°-111° C.

EXAMPLE 98 3-Pyridinecarboxylic acid,2-(difluoromethyl)-5-(4,5-dihydro-2-thiazolyl)-6-(1-methylethyl)-4-(2-methylpropyl)-,methyl ester

A solution of 17 g (40 mmol) of the crude pyridinedicarboxylate preparedas in Example 97 and 7 ml of tri-ethylamine in 160 ml of ethanol washydrogenolyzed at ambient temperature and 2 atmospheres of hydrogenpressure in the presence of 3 g of 5% pallalium on charcoal for 18hours. The suspension was filtered through celite and concentrated.Water and CH₂ Cl₂ were added and the phases were separated. The CH₂ Cl₂layer was washed with water, dried, and concentrated. Flashchromatography on silica gel (2% ethyl acetate/cyclohexane gave 14 g(91%) of 3,5-pyridinedicarboxylic acid,2-(difluoromethyl)-6-(1-methylethyl)-4-(2-methylpropyl),5-(1,1-dimethylethyl) 3-methyl ester as a colorless oil, n_(D) ²⁵=1.4713.

A solution of 5.4 g (14 mmol) of this material in 25 ml oftrifluoroacetic acid was stirred at room temperature for 18 hours, afterwhich the trifluoroacetic acid was removed. Water and CH₂ Cl₂ wereadded, and the phases were separated. The organic layer was washed withwater and then brine, then dried and concentrated. The resultingmonoacid in 30 ml of oxalyl chloride containing 3 drops of DMF washeated at reflux for 6 hours, then the excess oxalyl chloride wasremoved in vacuo, giving the crude monoacid chloride.

The crude acid chloride in 30 ml of CH₂ Cl₂ (9.4 g, 27 mmol) was addedto a solution of 12 g of 2-aminoethanol and 4 mL of triethylamine in 50ml of CH₂ Cl₂ at 0° C. The solution was stirred at room temperature for2 hours Water was added, then the organic layer was separated, washedwith water and then brine, dried, and concentrated. Flash chromatographyon silica gel (50% ethyl acetate/cyclohexane) gave 7 g (70%) of whitesolid (the 5-(2-hydroxyethyl) amide), m.p. 108°-112° C.

A reaction mixture of 4 g (11 mmol) of the N-2-hydroxyethylamide and 2.6g of phosphorous pentasulfide in 6.0 ml of xylene was heated underreflux for 18 hours. Ether and saturated NaHCO₃ solution were added. Theorganic layer was separated, washed with water, brine, dried andconcentrated. Flash chromatography on silicagel (6%ethylacetatecyclohexane) gave 0.4 (10%) of brown solid. m.p. 80°-86° C.

                                      TABLE 2                                     __________________________________________________________________________    Example                                                                       No.  Compound               M.P./B.P.                                                                           n.sub.D .sup.25                             __________________________________________________________________________     99  3-Pyridinecarboxamide, 2-(difluoromethyl)-                                                           183-185° C.                                     5-(4,5-dihydro-2-thiazolyl)-4-(2-methyl-                                      propyl)-6-(trifluoromethyl)-                                             100  3-Pyridinecarboxamide, 2-(difluoromethyl)-                                                           111-114° C.                                     5-(4,5-dihydro-2-thiazolyl)-N,N-dimethyl-4-                                   (2-methylpropyl)-6-(trifluoromethyl)-                                    101  Pyridine, 2-(difluoromethyl)-5-(4,5-dihydro-                                                         152-154° C.                                     2-thiazolyl)-4-(2-methylpropyl)-3-(1-methyl-                                  1H-tetrazol-5-yl)-6-(trifluoromethyl)-                                   102  3-Pyridinecarboxylic acid, 6-(difluoromethyl)-                                                             1.4778                                           4-(2-methylpropyl)-5-(5-oxazolyl)-2-(trifluoro-                               methyl)-, methyl ester                                                   103  3-Pyridinecarboxylic acid, 2-(difluoromethyl)-                                                             1.5025                                           5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-                                                            120° C. @ 0.2 mm                          6-(trifluoromethyl)-, 2-propynyl ester                                   104  3-Pyridinecarboxylic acid, 2-(difluoromethyl)-                                                             1.4935                                           5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-                                                            145° C. @ 0.2 mm                          6-(trifluoromethyl)-, 2-(2-methoxyethoxy)                                     ethyl ester                                                              105  3-Pyridinecarbothioic acid, 6-(difluoromethyl)-                                                      62-63° C.                                       5-[5-(1-methylethyl)-1,3,4-oxadiazol-2-yl]-4-                                 (2-methylpropyl)-2-(trifluoromethyl)-, S-methyl                               ester                                                                    106  3-Pyridinecarbothioic acid, 6-(difluoromethyl)-                                                            1.4996                                           5-(5-ethyl-1,3,4-oxadiazol-2-yl)-4-(2-methyl-                                                               145° C. @ 0.35 mm                        propyl)-2-(trifluoromethyl)-, S-methyl ester                             107  3-Pyridinecarboxylic acid, 2-(difluoromethyl)-                                                       110-111° C.                                     4-(2-methylpropyl)-5-(1-methyl-1H-tetrazol-5-yl)-                             6-(trifluoro-methyl)-, methyl ester                                      108  3-Pyridinecarboxylic acid, 6-(fluoromethyl)-5-                                                       63-64° C.                                       (4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-2-                               (trifluoromethyl)-, methyl ester                                         109  3-Pyridinecarboxylic acid, 2-(difluoromethyl)-                                                             1.4612                                           5-(1,3-dioxan-2-yl)-4-(2-methylpropyl)-6-(tri-                                fluoromethyl)-, methyl ester                                             110  3-Pyridinecarboxylic acid, 2-(difluoromethyl)-                                                             1.4919                                           5-(4,5-dihydro-2-thiazolyl)-4-(2-methylpropyl)-                               6-(trifluoromethyl)-, 2-fluoroethyl ester                                111  3-Pyridinecarboxylic acid, 6-(difluoromethyl)-                                                       129-130° C.                                     4-(2-methylpropyl)-5-(1,3-oxathiolan-2-yl)-                                   2-(trifluoromethyl)-, methyl ester                                       112  3-Pyridinecarboxylic acid, 6-(difluoromethyl)-                                                       119-120° C.                                     5-(1,3-dioxolan-2-yl)-4-(2-methylpropyl)-2-                                   (trifluoromethyl)-, methyl ester                                         __________________________________________________________________________

PRE-EMERGENT HERBICIDE EXAMPLES

As noted above, compounds of this invention have been found to beeffective as herbicides, particularly pre-emergent herbicides. Tables Aand B summarize results of tests conducted to determine the pre-emergentherbicidal activity of the compounds of this invention. The herbicidalratings used in Tables A and B were assigned according to a scale basedon the percent inhibition of each plant species. The herbicide ratingsymbols in Tables A and B are defined as follows:

    ______________________________________                                        % Inhibition        Rating                                                    ______________________________________                                         0-24               0                                                         25-49               1                                                         50-74               2                                                          75-100             3                                                         Not planted         -- or a blank                                             ______________________________________                                    

Species planted, no data N Where necessary, footnotes are shown at theend of the table.

For some compounds of this invention data were originally recorded aspercent inhibition (or control) in ten percent increments. Where thissystem was used, the percentages have been mathematically converted tothe above equivalent system using the correlation table above.

PRE-EMERGENT ACTIVITY ON WEEDS

One set of pre-emergent tests was conducted as follows:

Topsoil was placed in a pan and compacted to a depth of 0.95 to 1.27 cm.from the top of the pan. A predetermined number of seeds of each ofseveral monocotyledonous and dicotyledonous annual plant species and/orvegetative propagules of various perennial plant species were placed ontop of the soil. The soil required to level fill a pan after seeding oradding vegetative propagules was weighed into another pan. A knownamount of the test compound dissolved or suspended in an organic solventor water and applied in acetone or water as a carrier was thoroughlymixed with this cover soil, and the herbicide/soil mixture was used as acover layer for the previously prepared pan. In Table A below the amountof active ingredient was eqivalent to an application rate of 11.2 kg/ha.After treatment, the pans were moved to a greenhouse bench where theywere watered as needed to give adequate moisture for germination andgrowth.

Approximately 10-14 days (usually 11 days) after planting and treating,the pans were observed and the results recorded. In some instances, asecond observation was made approximately 24-28 days after seeding andtreating, and these observations are indicated in the following tablesby a "pound" sign (#) immediately following the Example number.

The plant species usually regarded as weeds which were utilized in oneset of pre-emergent activity tests, the data for which are shown inTable A, are identified by letter headings printed diagonally above thecolumns according to the following legend:

CATH--Canada thistle*

RHQG--Quackgrass*

COBU--Cocklebur

RHJG--Rhizome Johnsongrass*

VELE--Velvetleaf

DOBR--Downy Brome

MOGL--Morningglory

BYGR--Barnyardgrass

COLQ--Common Lambsquarters

ANBG--Annual Bluegrass

PESW--Pennsylvania Smartweed

SEJG--Seedling Johnsongrass

YENS--Yellow Nutsedge*

INMU--Indian Mustard

WIBW--Wild Buckwheat

In Table A, the first column is the application rate of the compoundbeing tested in kg/ha.

                                      TABLE A                                     __________________________________________________________________________    Ex.  Rate                                                                     No.  kg/ha                                                                             Yens                                                                             Anbg                                                                              Sejg                                                                             Dobr                                                                              Bygr                                                                              Mogl                                                                              Cobu                                                                              Vele                                                                             Inmu                                                                             Wibw                                                                              Cath                                                                              Colq                                                                             Pesw                                                                             Rhqg                                                                              Rhjg               __________________________________________________________________________     1   11.2100                                                                           1         0   3   2   0   2         1   3  2  1   N                   2   11.2100                                                                           3         3   3   3   2   3         3   3  3  3   0                   3   11.2100                                                                           3         3   3   3   3   3         3   3  3  3   3                   4   11.2100                                                                           1         3   3   3   0   3         1   3  3  2   0                   5   11.2100                                                                           2         3   3   3   2   3         3   3  3  3   3                   6   11.2100                                                                           3         3   3   3   2   3         3   3  3  3   0                   7   11.2100                                                                           3         3   3   3   1   3         1   3  3  3   0                   8   11.2100                                                                           1         --  3   2   0   1         3   3  2  3   0                   9   11.2100                                                                           3         --  3   3   2   3         3   3  3  3   3                  10   11.2100                                                                           3         3   3   3   3   3         3   3  3  3   3                  11   11.2100                                                                           1         3   3   3   1   3         3   3  3  3   3                  12   11.2100                                                                           0         1   3   0   0   0         0   3  3  0   0                  13   11.2100                                                                           1         2   3   2   0   0         0   3  3  3   3                  14   11.2100                                                                           2         3   3   1   0   3         0   3  3  2   0                  15   11.2100                                                                           1         3   3   3   3   3         3   3  3  3   3                  16   11.2100                                                                           0         1   3   0   0   0         0   2  1  0   0                  17   11.2100                                                                           3         3   3   3   3   3         3   3  3  3   3                  18   11.2100                                                                           3         3   3   3   3   3         3   3  3  3   3                  19   11.2100                                                                           3         3   3   3   2   3         3   3  3  3   3                  20   11.2100                                                                           0         3   3   3   0   3         3   3  3  3   0                  21   11.2100                                                                           3         3   3   3   2   3         0   3  3  3   3                  22   11.2100                                                                           2         3   3   3   0   3         2   3  3  3   0                  23   11.2100                                                                           2         3   3   3   1   3         0   3  3  3   0                  24   11.2100                                                                           0         3   3   0   0   0         0   3  2  3   0                  25   11.2100                                                                           0         1   3   1   0   2         3   3  3  3   1                  26   11.2100                                                                           1         3   3   3   0   3         0   3  3  1   0                  27   11.2100                                                                           3         3   3   3   2   3         --  3  3  3   3                  28   11.2100                                                                           3         3   3   3   3   3         3   3  3  3   3                  29   11.2100                                                                           1         3   3   3   0   3         3   3  3  3   0                  30   11.2100                                                                           2         3   3   3   1   3         3   3  3  3   0                  31   11.2100                                                                           2         3   3   3   0   3         3   3  3  3   0                  32   11.2100                                                                           3         3   3   3   1   3         3   3  3  3   2                  33   11.2100                                                                           1         3   3   3   0   3         1   3  3  3   1                  34   11.2100                                                                           3         3   3   3   3   3         3   3  3  3   3                  35   11.2100                                                                           2         3   3   3   2   3         3   3  3  3   3                  36   11.2100                                                                           3         3   3   3   3   3         3   3  3  3   3                  37   11.2100                                                                           2         3   3   3   2   3         3   3  3  3   3                  38   11.2100                                                                           3         3   3   3   2   3         3   3  3  3   0                  39   11.2100                                                                           0         3   3   3   0   3         0   3  3  2   0                  40   11.2100                                                                           1         3   3   3   2   3         1   3  3  3   3                  41   11.2100                                                                           3         3   3   3   3   3         3   3  3  3   3                  42   11.2100                                                                           0         3   3   3   1   3         3   3  3  3   0                  43   11.2100                                                                           2         3   3   3   2   3         3   3  3  3   2                  44   11.2100                                                                           3         3   3   3   3   3         3   3  3  3   3                  45   11.2100                                                                           1         --  3   3   3   3         1   3  3  3   0                  46   11.2100                                                                           3         --  3   3   1   3         3   3  3  3   3                  47   11.2100                                                                           3         3   3   3   1   1         3   3  3  3   0                  48   11.2100                                                                           3         3   3   3   0   3         3   3  3  3   3                  49   11.2100                                                                           2         3   3   3   0   2         0   3  3  3   3                  50   11.2100                                                                           1         1   3   3   0   3         2   3  3  2   0                  51   11.2100                                                                           2         3   3   3   0   2         3   3  3  3   3                  52   11.2100                                                                           3         3   3   3   0   3         3   3  3  3   3                  53   11.2100                                                                           0         0   3   0   0   0         3   3  1  0   0                  54   11.2100                                                                           0         1   3   3   0   3         0   3  2  0   3                  55   11.2100                                                                           3         3   3   3   2   3         0   3  3  3   0                  56   11.2100                                                                           1         3   3   3   0   1         0   3  3  3   3                  57   11.2100                                                                           3         3   3   3   3   3         3   3  3  3   0                  58   11.2100                                                                           3         3   3   3   0   3         0   3  3  3   3                  59   11.2100                                                                           2         3   3   3   3   3         3   3  3  3   0                  60   11.2100                                                                           3         3   3   3   1   3         3   3  3  3   3                  61   11.2100                                                                           0         0   3   0   0   0         0   0  0  0   0                  62   11.2100                                                                           1         2   3   3   1   2         0   3  3  3   0                  63   11.2100                                                                           1         1   3   3   2   3         1   3  3  3   0                  64   11.2100                                                                           0         3   3   3   3   3         3   3  3  3   0                  65   11.2100                                                                           2         3   3   3   0   3         0   3  3  3   0                  66   11.2100                                                                           3         3   3   3   3   3         2   3  3  3   0                  67   11.2100                                                                           1         3   3   3   1   3         3   3  3  3   0                  68   11.2100                                                                           0         2   3   2   0   1         0   3  3  2   0                  69   11.2100                                                                           0         3   3   2   1   2         3   3  3  3   1                  70   11.2100                                                                           1         3   3   3   2   3         3   3  3  3   0                  71   11.2100                                                                           0         3   3   3   3   3         3   3  3  3   3                  72   11.2100                                                                           3         3   3   3   2   3         3   3  3  3   3                  73   11.2100                                                                           0         0   3   0   0   0         0   0  0  0   0                  74   11.2100                                                                           0         0   0   0   0   0         0   1  0  0   0                  75   11.2100                                                                           0         0   0   0   0   0         0   0  0  0   0                  76   11.2100                                                                           0         0   0   0   0   0         0   3  0  0   0                  77   11.2100                                                                           0         3   3   2   0   2         0   3  3  1   1                  78   11.2100                                                                           2         3   3   3   0   3         3   3  3  3   3                  79   11.2100                                                                           1         3   3   3   2   3         0   3  3  3   0                  80   11.2100                                                                           3         3   3   3   0   3         3   3  3  3   3                  81   11.2100                                                                           2         2   3   3   0   3         3   3  3  3   3                  82   11.2100                                                                           3         3   3   3   3   3         3   3  3  3   0                  83   11.2100                                                                           2         3   3   3   3   3         3   3  3  3   3                  84   11.2100                                                                           2  3   3  3   3   3   0   2  3  3                                    85   11.2100                                                                           0  2   0  0   3   0   0   0  0  0                                    86   11.2100                                                                           0  3   3  2   3   0   0   2  2  1                                    87   11.2100                                                                           1  3   3  3   3   3   0   3  3  3                                     88* 11.2100                                                                           0         2   3   3   0   2         0   3  N  0   0                  89   11.2100                                                                           0         0   3   1   0   0         0   2  N  1   0                  90   11.2100                                                                           0  0   0  0   0   0   0   0  0  0                                     91  11.2100                                                                           1         1   3   3   2   3         3   3  N  1   0                  92   11.2100                                                                           2  3   3  3   3   3   0   3  3  3                                     93@ 11.2100                                                                           2  3   3  3   3   3   2   3  3  3                                    94   11.2100                                                                           3  3   3  3   3   3   2   3  3  3                                    95   11.2100                                                                           3  3   3  3   3   3   3   3  3  3                                     96@ 11.2100                                                                           1  3   3  3   3   3   1   3  3  2                                      @  11.2100                                                                           1  3   3  3   3   3   1   3  3  2                                    97   11.2100                                                                           0  3   3  3   3   1   1   1  3  3                                    98   11.2100                                                                           2  3   3  3   3   3   2   3  3  3                                    99   11.2100                                                                           0  3   2  2   3   0   0   0  1  0                                    100  11.2100                                                                           0  3   3  0   3   1   0   1  2  2                                    101  11.2100                                                                           0  3   0  0   3   1   1   2  1  2                                    102  11.2100                                                                           1  3   3  3   3   3   3   3  3  3                                    103  11.2100                                                                           2         3   3   3   1   3         3   3  N  3   0                  104  11.2100                                                                           0         0   3   2   0   2         0   3  N  0   0                  105  11.2100                                                                           0         0   3   0   0   0         0   1  N  0   0                  106* 11.2100                                                                           0         3   3   3   0   3         3   3  N  3   0                  107  11.2100                                                                           0  2   3  3   3   1   0   1  1  1                                    108  11.2100                                                                           2  3   3  3   3   3   0   3  3  3                                     109@                                                                              11.2100                                                                           2  3   3  3   3   3   2   3  3  3                                     110+                                                                              11.2100                                                                           2  3   3  3   3   3   3   3  3  3                                    111  11.2100                                                                           0  3   3  2   3   3   0   3  3  3                                    112  11.2100                                                                           1  3   3  3   3   3   0   3  3  2                                    __________________________________________________________________________     * POOR SMARTWEED GERMINATION                                                    NO TO POOR SMARTWEEK GERMINATION.                                           @ DAMPING OFFIM,WB. POOR GERMINATIONWB.                                       + DAMPING OFFIM,WB POOR GERMINATIONCB                                    

PRE-EMERGENCE ACTIVITY ON WEEDS AND CROPS

In another set of tests, the pre-emergence activity of compounds of thisinvention was tested on weeds in the presence of crop plants. In thesetests the following procedure was used:

Topsoil was sieved to pass through a 1/2 inch (1.27 cm) screen.Fertilizer was added to the topsoil in some of the tests, while intesting other compounds the fertilizer was omitted. The mixture was thensterilized by exposure to methyl bromide or by heating.

The topsoil mixture was placed in an aluminum pan and compacted to adepth of about 1.27 cm. from the top of the pan. A predetermined numberof seeds of each of several monocotyledonous and dicotyledonous plantspecies and where noted vegetative propagules of various perennial plantspecies. The soil required to level fill a pan after seeding or addingvegetative propagules was weighed into another pan. A known amount ofthe test compound was dissolved or suspended in acetone or a suitableorganic solvent as a 1% solution or suspension and applied to the coversoil using a sprayer at the desired rate. The spray was thoroughly mixedwith this cover soil, and the herbicide/soil mixture was used as a coverlayer for the previously prepared pan. Untreated soil was used as acover layer for control pans. Alternatively, the pans may be coveredwith the soil layer and the spray solution uniformly applied to the soilsurface. When this latter method was used, the statement "surfaceapplication" accompanies the test data. In Table B below the amount ofactive ingredient applied is shown in the Table. After treatment,thepans were moved to a greenhouse bench. Moisture was supplied to each panas needed for germination and growth. Growth of each species wasobserved and corrective measures (greenhouse fumigation, insecticidetreatment, and the like) were applied as needed

Approximately 10-14 days (usually 11 days) after planting and treating,the pans were observed and the results recorded In some instances, asecond observation is made (usually 24-28 days after seeding andtreating, although this time interval was at the discretion of theobserver), and these observations are indicated in the following tablesby a "pound" sign (#) immediately following the Example number.

The pre-emergence data for weeds in the presence of crop plants is shownin the following Table B. In these tests, the plants are identifiedaccording to the following column headings printed diagonally above eachcolumn, the first column being the rate of application of the testcompound in kg/ha:

    ______________________________________                                        SOBE - Soybean      VELE - Velvetleaf                                         SUBE - Sugarbeet    DOBR - Downy Brome                                        WHEZ - Wheat        PRMI - Proso Millet                                       RICE - Rice         BYGR - Barnyardgrass                                      GRSO - Grain Sorghum                                                                              LACG - Large Crabgrass                                    COBU - Cocklebur    GRFT - Green Foxtail                                      WIBW - Wild Buckwheat                                                                             CORN - Corn                                               NOGL - Morningglory COTZ - Cotton                                             HESE - Hemp Sesbania                                                                              RAPE - Oilseed Rape                                       COLQ - Common Lambsquarters                                                                       JIWE - Jimsonweed                                         PESW - Pennsylvania Smartweed                                                 ______________________________________                                    

    TABLE B      Ex.  Rate                      No. kg/ha Sobe Cotz Rape Cobu Wibw Mogl     Hese Jiwe Vele Whez Rice Grso Corn Dobr Prmi Bygr Lacg Grft Sube Colq     Pesw        1 5.6050 1   0 0 2  0  0 0 2 2 0 0 3 3 3 3 0 0 3  1.1210 0   N 1 0 1     0 0 0 0 0 0 2 0 0 0 0 N 1  0.5605 0   N 0 N 0  0 0 0 0 0 0 0 0 1 0 0 2 2      0.2803 0   0 0 0 2  0 0 0 1 0 0 0 0 3 0 0 0 N  0.1401 N   0 0 0 0  0 0     0 0 0 0 0 0 0 0 2 1 2  0.0701 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 2  2     5.6050 2   0 3 3 3  2 3 3 3  3 3 3 3  3 3 3  1.1210 0   0 3 1 1  1 1 2 2      3 3 3 3  0 3 3  0.2803 0   0 0 0 0  1 0 2 1  0 0 2 3  0 2 0  0.0561 0     0 0 0 0  0 0 0 0  0 0 0 1  0 0 0  0.0112 0   0 0 0 0  0 0 0 0  0 0 0 0     0 0 0  3 5.6050 3   2 3 3 3  3 3 3 3  3 3 3 3  3 3 3  1.1210 3   1 3 3 3      2 3 3 3  3 3 3 3  3 3 3  0.2803 2   1 3 2 2  2 2 3 3  3 3 3 3  2 3 3     0.0561 0   0 2 1 2  1 1 3 1  0 2 3 3  1 2 2  0.0112 0   0 0 0 1  0 0 0 0      0 2 3 3  0 0 1  0.0056 0   0 2 0 0  0 0 0 1  0 0 0 2  1 0 0  0.0011 0     0 1 0 0  0 0 0 0  0 0 0 0  0 0 0  4 5.6050 3   0 3 2 2  2 3 3 2  3 3 3 3      3 3 3  1.1210 3   0 1 0 1  0 1 1 0  2 3 3 3  0 3 2  0.2803 0   0 0 0 0     0 0 1 0  0 0 3 2  0 2 0  0.0561 0   0 0 0 0  0 0 0 0  0 0 0 1  0 0 0  5     5.6050 3   0 3 3 3  3 3 3 3  3 3 3 3  3 3 3  1.1210 3   0 3 3 3  3 3 3 3      3 3 3 3  3 3 3  0.2803 0   0 1 0 2  2 1 0 3  3 2 3 3  2 3 3  0.0561 0     0 0 0 0  0 0 0 0  0 1 3 3  0 0 0  0.0112 0   0 0 0 0  0 0 0 0  0 0 0 2     0 0 0  6 5.6050 3   1 3 2 3  3 3 0 3  3 3 3 3  3 3 3  1.1210 2   0 2 2 2      2 1 0 2  2 3 3 3  3 3 3  0.5605 0   0 1 0 1  1 1 0 0  1 3 3 3  1 3 3     0.2803 0   0 1 0 0  0 0 0 0  0 2 3 3  2 2 1  0.1401 0   0 N 0 0  0 0 0 0      0 2 3 2  1 2 1  0.0701 0   0 0 0 0  0 0 0 0  0 0 1 2  0 1 0  0.0350 0     0 0 0 0  0 0 0 0  0 0 0 0  0 1 0  7 5.6050 3   0 3 2 3  3 2 2 3  3 3 3 3      3 3 3  1.1210 0   0 3 1 2  2 1 1 3  2 3 3 3  3 3 3  0.5605 0   0 1 1 2     2 1 0 2  2 3 3 3  3 3 3  0.2803 0   0 0 0 0  1 1 0 0  1 2 3 3  2 3 3     0.1401 0   0 0 0 0  0 0 0 0  2 N 3 3  2 3 2  0.0701 0   0 0 0 0  0 0 0 0      1 0 3 3  1 2 0  0.0350 0   0 0 0 0  0 0 0 0  N 0 3 2  N N 1  0.0175 0     0 0 0 0  0 0 0 0  0 0 3 2  1 2 1  8* 5.6050 1   1 0 2 1  1 2 2 3 2 3 3 3     3 3 2 3 2   * 1.1210 0   0 0 1 1  0 0 0 0 0 1 2 3 3 3 1 2 1   * 0.5605 0       0 0 0 1  0 0 0 0 0 0 2 2 2 3 0 3 0   * 0.2803 0   0 0 0 0  0 0 0 0 0 0     0 1 2 1 0 0 0   * 0.1401 0   0 0 0 0  0 0 0 0 0 0 0 0 1 0 0 0 0   *     0.0701 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 N 0  9  5.6050 2   1 3 3 3  3     3 3 3 3 3 3 3 3 3 3 3 3     1.1210 2   0 3 3 3  3 2 3 3 2 3 3 3 3 3 3 3     3     0.5605 0   0 3 3 3  3 2 2 3 2 3 3 3 3 3 3 3 3     0.2803 0   0 3 1     3  3 2 3 3 1 1 3 3 3 3 3 3 3     0.1401 0   0 0 1 2  2 2 1 3 1 2 3 3 3 3     2 3 3     0.0701 0   0 0 0 0  1 0 1 1 0 1 3 3 3 3 1 3 3     0.0350 0   0     0 0 0  0 0 0 1 1 2 3 3 3 3 1 1 2     0.0175 0   0 0 0 0  0 0 0 0 0 0 0 1     2 1 0 0 0     0.0087 0   0 0 0 0  0 0 0 0 0 0 0 0 1 0 0 0 0  10 5.6050 3       1 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 2   0 1 1 2  3 3 3 3 1 3 3     3 3 3 3 3 3  0.5605 2   0 1 1 3  3 2 2 3 0 3 3 3 3 3 2 3 3  0.2803 1   0     1 0 2  2 1 3 2 0 2 3 3 3 3 1 3 3  0.1401 0   0 0 0 3  3 1 1 3 0 3 3 3 3     3 0 3 3  0.0701 0   0 0 0 1  1 0 2 1 0 2 3 3 3 3 0 1 3  0.0350 0   0 0 0     1  0 0 1 2 0 0 3 3 2 3 0 1 1  0.0175 0   0 0 0       0 0 0 1 0 0 0 2 2 2 0 0 0  0.0087 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0     0  0.0044 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  11 5.6050 2   0 1 2 3     2 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 1   0 1 0 2  2 2 3 3 1 3 3 3 3 3 3 3 3      0.5605 0   0 0 0 1  1 2 3 3 0 3 3 3 3 3 1 3 3  0.2803 0   0 0 0 1  0 1     3 2 0 2 3 3 3 3 1 3 3  0.1401 0   0 0 0 0  0 0 2 2 0 2 3 3 3 3 0 2 2     0.0701 0   0 0 0 0  0 0 0 1 0 1 0 3 2 2 1 0 1  0.0350 0   0 0 0 0  0 0 0     0 0 0 0 0 1 1 0 0 0  0.0175 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0     0.0087 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  12 5.6050 0   0 0 0 0  0     1 1 3 0 3 3 3 3 3 0 1 1  1.1210 0   0 0 0 0  0 0 0 0 0 3 1 1 2 2 0 0 0     0.5605 0   0 1 0 0  0 0 1 0 0 1 1 1 3 1 0 0 0  0.2803 0   0 0 0 0  0 0 0     0 0 0 1 1 1 2 0 0 0  13 2.8025 0   0 1 0 1  1 1 1 2 0 2 3 3 1 3 0 3 0     1.1210 0   0 1 0 0  0 0 2 1 0 1 3 3 3 2 0 0 0  0.5605 0   0 0 0 0  0 0 0     0 0 1 1 0 0 0 0 0 0  0.2803 0   0 0 0 0  0 0 0 0 0 0 0 0 2 2 0 0 0     0.1401 0   0 0 0 0  0 0 0 0 0 2 0 0 0 0 0 0 0  0.0701 0   0  N' 0 0  0 0     0 0 0 0 0 0 0 0 N N 0  0.0350 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0     0.0175 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  14 5.6050 0   0 2 1 2  3     0 0 3 0 2 3 3 2 0 3 3 3  1.1210 0   0 1 0 1  2 0 0 1 0 0 3 2 0 0 0 1 3     0.5605 0   0 0 0 0  0 0 0 0 0 0 3 2 0 0 0 0 2  0.2803 0   0 0 0 0  0 0 0     0 0 0 1 0 0 0 0 0 0  0.1401 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0     0.0701 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  15 5.6050 3   3 3 3 3  3     3 3 3 3 3 3 3 3 3 3 3 3  1.1210 3   0 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3     0.5605 3   1 3 3 3  3 3 3 3 3 3 3 3 3 3 2 3 3  0.2803 0   0 2 2 3  3 1 2     3 2 3 3 3 3 3 3 3 3  0.1401 0   0 3 3 3  2 0 2 3 2 3 3 3 3 3 1 1 3     0.0701 0   0 1 2 3  2 1 3 2 1 1 3 3 3 3 1 1 3  0.0350 0   0 0 0 1  1 0 2     1 2 2 2 3 3 3 0 1 3  0.0175 0   0 0 0 1  0 0 2 0 0 1 2 3 3 3 0 0 3     0.0087 0   0 0 0 0  0 0 0 0 0 0 0 0 3 2 0 0 1  16 5.6050 1   0 0 2 1  2     3 3 2 0 3 3 3 3 3 2 1 1  1.1210 0   0 2 0 0  0 0 0 1 0 2 1 2 1 1 0 0 0     0.5605 0   0 0 1 0  0 0 0 0 0 1 1 0 2 1 0 0 1  0.2803 0   0 2 1 0  0 0 0     0 0 N 0 1 0 0 0 0 2  17 5.6050 3   3 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3     1.1210 3   0 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  0.5605 0   1 3 3 2  3 3 3     3 1 3 3 3 3 3 2 3 3  0.2803 0   0 3 2 1  1 1 3 3 0 2 3 3 3 3 2 3 3     0.1401 0   0 0 0 2  2 0 2 3 1 2 3 3 3 3 N 3 3  0.0701 0   0 0 0 1  2 0 2     2 0 2 3 3 3 3 0 2 3  0.0350 0   0 0 0 0  0 0 2 0 0 0 3 3 3 3 0 0 3     0.0175 0   0 0 0 0  0 0 1 0 0 0 0 3 3 3 N N 0  0.0087 0   0 N 0 0  0 0 0     0 0 0 0 0 1 2 0 N 0  0.0044 0   0 0 0 0  0 0 0 0 0 0 0 0 3 2 N N 0  18     5.6050 3   3 3 3 3  3 3 3 3  3 3 3 3  3 3 3  1.1210 3   2 3 3 3  3 3 3 3      3 3 3 3  3 3 3  0.2803 2   0 3 3 3  2 2 3 3  3 3 3 3  3 3 3  0.0561 0     0 2 3 2  2 2 3 2  0 3 3 3  2 3 2  0.0112 0   0 2 2 2  0 0 1 2  1 3 3 3     0 3 1  0.0056 0   0 0 0 0  0 0 0 0  1 3 3 3  0 1 1  0.0011 0   0 0 0 0     0 0 0 0  0 0 0 1  0 0 0  19 5.6050 3   1 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3     3  1.1210 2   1 3 2 3  3 3 3 3 3 3 3 3 3 3 3 3 3  0.5605 1   0 3 3 3  3     3 3 3 3 3 3 3 3 3 3 3 3  0.2803 0   0 3 1 1  3 2 2 2 0 3 3 3 3 3 3 3 3     0.1401 0   0 0 0 1  0 1 0 1 0 3 3 3 3 3 1 3 0  0.0701 0   0 0 0 0  0 3 0     1 0 3 3 3 3 3 N 3 1  0.0350 0   0 1 0 0  0 0 0 0 0 3 0 3 3 3 N 3 N     0.0175 N   0 1 N 0  0 N 0 N 0 2 0 3 3 3 0 3 0  0.0087 0   0 N 0 0  0 0 0     0 0 3 0 0 3 0 N N N  20 5.6050 3   1 3 3 3  3 3 3 2 2 3 3 3 3 3 3 3 3     1.1210 0   0 3 1 1  0 3 1 0 0 3 3 3 3 3 3 3 3  0.5605 0   0 1 0 0  1 1 1     0 0 3 3 3 3 3 3 3 3  0.2803 0   0 3 0 0  0 0 0 0 0 1 1 2 3 3 1 3 3     0.1401 0   0 0 0 0  0 0 0 0 0 2 1 1 3 1 N 3 3  0.0701 0   0 0 0 0  0 0 0     0 0 1 0 0 3 1 1 3 1  0.0350 0   1 N 0 0  0 0 0 0 0 N 0 0 3 1 1 3 1     0.0175 0   0 0 0 0  0 0 0 0 0 1 0 0 0 0 N 3 0  21 5.6050 3   3 3 3 3  3     3 3 3 3 3 3 3 3 3 3 3 3  1.1210 2   0 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3     0.5605 2   0 3 3 2  2 3 3 3 1 3 3 3 3 3 3 3 3  0.2803 0   1 1 1 2  2 2 3     3 0 3 3 3 3 3 2 2 3  0.1401 0   0 2 0 1  2 3 3 2 0 3 3 3 3 3 1 3 3     0.0701 0   0 1 0 0  0 2 3 2 0 3 3 3 3 3 1 2 2  0.0350 0   0 1 0 0  0 1 1     1 0 1 1 2 3 3 0 1 1  0.0175 0   0 0 0 0  0 0 0 0 0 3 3 2 1 2 0 1 0     0.0087 0   0 0 0 0  0 0 0 0 0 1 0 0 0 0 0 0 0  22 5.6050 0   0 0 0 1  0     0 0 0 0 0 0 1 0 0 0 1 0  5.6050 0   1 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3     1.1210 0   0 3 2 3  3 3 3 1 3 3 3 3 3 3 3 3 3  1.1210 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 0 0  0.5605 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0     0.5605 0   0 3 1 3  3 3 3 2 0 3 3 3 3 3 1 3 3  0.2803 0   0 0 2 1  1 2 2     1 0 3 3 3 3 3 1 3 3  0.2803 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0     0.1401 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  0.1401 0   0 0 0 0  0 0 0     0 0 2 2 3 3 2 0 3 3  0.0701 0   0 0 1 0  0 1 0 0 0 2 2 1 0 2 1 2 1     0.0701 0   0 0 N 0  0 N N 0 N N N N 0 N 0 0 0  0.0350 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 0 0  0.0350 0   1 1 1 0  0 0 0 0 0 1 0 2 0 1 0 1 0     0.0175 0   0 0 0 0  0 0 0 0 0 1 0 0 1 0 0 1 0  0.0175 0   0 0 0 0  0 0 0     0 0 N 0 0 0 N N N 0  0.0087 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  23     5.6050 3   1 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 0   0 3 1 1  2 3 3     3 1 3 3 3 3 3 3 3 3  5.5605 0   0 3 1 2  1 3 1 2 0 2 3 3 3 3 3 3 3     0.2803 0   0 3 N N  N 3 3 3 0 3 3 3 3 3 N 3 3  0.1401 0   0 1 0 1  2 1 1     2 0 0 3 3 3 3 1 N 2  0.0701 0   0 0 0 0  0 0 0 0 0 3 2 3 3 3 0 3 1     0.0350 0   0 N 0 N  N 0 0 0 0 2 0 3 3 2 N N 0  24 5.6050 0   0 0 3 1  3     0 1 2 0 2 3 3 3 3 0 0 0  1.1210 0   1 0 0 N  0 0 0 0 0 0 0 0 1 0 N 0 N     0.5605 0   0 0 0 0  0 0 0 0 0 0 0 0 1 0 0 0 0  0.2803 0   1 N 0 0  0 0 0     0 0 0 0 0 0 0 0 N 0  0.1401 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0     0.0701 0   1 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  25 5.6050 1   0 3 3 3  3     3 3 3 3 3 3 3 3 3 3 3 3  1.1210 0   0 3 0 0  1 2 2 2 2 2 3 3 3 3 1 3 3     0.5605 0   0 1 2 1  2 1 2 3 1 2 3 3 3 3 1 3 3  0.2803 N   0 0 2 0  1 1 0     2 2 2 3 3 3 3 1 3 3  0.1401 0   0 1 1 0  0 0 0 1 0 0 2 1 3 1 1 2 2     0.0701 0   0 0 0 0  0 0 0 1 0 0 1 2 3 1 0 0 0  0.0350 0   0 0 0 0  0 0 0     0 0 0 1 1 2 2 0 0 1  26 5.6050 0   0 3 1 1  2 3 2 2 2 3 3 3 3 3 3 3 3     1.1210 0   0 2 0 0  1 1 1 1 0 3 3 3 3 3 1 3 3  0.5605 0   0 1 0 0  1 0 0     1 0 3 3 3 3 3 0 3 2  0.2803 0   0 0 0 0  1 0 0 0 0 2 1 3 3 3 0 1 1     0.1401 0   0 N 0 0  0 0 0 0 0 3 1 3 3 3 N N N  0.0701 0   0 0 0 0  0 0 0     0 0 0 1 1 3 1 0 0 1  27 5.6050 3   1 3 3 3  3 3 3 3  3 3 3 3  3 3 3     1.1210 3   0 3 3 3  3 3 3 3  3 3 3 3  3 3 3  0.2803 0   0 1 2 1  2 2 1 3      3 3 3 3  3 3 3  0.0561 0   0 0 0 0  1 0 0 1  3 3 3 3  3 3 2  0.0112 0     0 2 0 0  0 2 0 0  3 0 0 3  2 2 1  0.0056 0   0 0 0 0  0 0 1 0  0 0 0 0     0 0 0  0.0011 0   0 0 0 0  0 0 0 1  0 0 0 0  0 0 0  28 5.6050 3   3 3 3     3  3 3 3 3  3 3 3 3  3 3 3  1.1210 3   1 3 3 3  3 3 3 3  3 3 3 3  3 3 3     0.2803 2   1 2 3 3  2 3 3 3  3 3 3 3  3 3 3  0.0561 1   N 3 2 2  2 0 2 3      3 3 3 3  1 3 2  0.0112 0   0 0 0 0  1 0 1 1  0 1 3 2  1 1 0  0.0056 0     0 1 1 1  0 0 1 0  0 1 1 2  1 2 1  29 5.6050 2   0 2 3 3  3 3 3 3  3 3 3     3  3 3 3  1.1210 0   0 3 2 2  2 0 2 3  3 3 3 3  3 3 3  0.2803 0   0 1 1     0  1 0 0 1  1 1 3 3  0 1 1  0.0561 0   0 0 0 0  0 0 0 0  0 0 0 2  0 0 0     30 5.6050 3   1 3 3 3  3 3 3 3  3 3 3 3  3 3 3  1.1210 3   0 2 3 3  2 3     3 3  3 3 3 3  3 3 3  0.2803 0   0 2 3 2  1 1 3 3  3 3 3 3  2 3 1  0.0561     0   0 0 2 2  0 0 1 2  1 3 3 3  2 3 1  0.0112 1   0 1 0 0  0 0 0 0  1 0 3     3  0 2 0  0.0056 0   0 0 1 0  0 0 1 1  0 0 1 2  1 1 1  31 5.6050 2   0 2     3 2  3 3 2 3  3 3 3 3  2 3 3  1.1210 1   0 0 1 1  0 0 0 0  0 3 2 3  0 3     2  0.2803 0   0 0 0 0  0 0 0 0  0 0 0 1  0 0 0  0.0561 0   0 0 0 0  0 0     0 0  0 0 0 0  0 0 0  32 5.6050 3   0 3 3 2  3 3 3 3  3 3 3 3  3 3 3     1.1210 2   0 1 3 2  1 3 1 2  3 3 3 3  2 3 3  0.2803 0   0 0 1 0  1 0 0 1      1 3 3 3  0 3 2  0.0561 0   0 0 0 0  0 0 0 0  0 1 0 1  0 1 0  0.0112 0     0 0 0 0  0 0 0 0  0 0 0 0  0 0 0  33 5.6050 3   0 3 3 3  2 3 3 3  3 3 3     3  3 3 3  1.1210 0   0 3 3 2  1 2 2 3  3 3 3 3  3 3 3  0.2803 0   0 0 1     1  0 0 1 1  2 3 3 3  1 3 2  0.0561 0   0 0 0 0  0 0 0 0  1 0 1 2  0 2 0     34 5.6050 3   3 3 3 3  3 3 3 3  3 3 3 3  3 3 3  1.1210 3   1 3 3 3  3 3     3 3  3 3 3 3  3 3 3  0.2803 3   0 3 3 3  3 2 2 3  3 3 3 3  3 3 3  0.0561     1   0 3 1 1  2 0 0 3  3 3 3 3  3 3 3  0.0112 0   0 0 1 0  0 0 0 0  0 1 3     3  1 1 0  0.0056 0   0 0 0 0  0 0 0 0  0 0 1 1  0 0 1  35 5.6050 3   3 3     3 3  3 3 3 3  3 3 3 3  3 3 3  1.1210 3   1 3 3 3  3 3 3 3  3 3 3 3  3 3     3  0.2803 1   0 3 2 1  2 1 1 3  3 3 3 3  2 3 3  0.0561 0   0 0 0 0  0 0     0 1  3 3 3 3  0 1 1  0.0112 0   0 0 0 0  0 0 0 0  0 1 3 3  0 0 0  0.0056     0   0 0 0 0  1 0 0 0  1 0 0 1  0 0 0  36 5.6050 3   1 3 3 3  3 3 3 3  3     3 3 3  3 3 3  1.1210 3   0 3 3 3  2 3 3 3  3 3 3 3  3 3 3  0.2803 1   0     3 3 1  2 2 2 1  3 3 3 3  3 3 3  0.0561 0   0 0 3 0  0 0 0 0  0 3 3 3  2     2 2  0.0112 0   0 0 1 0  0 0 0 0  0 0 1 2  0 0 0  37 5.6050 3   0 3 3 3     3 3 3 3  3 3 3 3  3 3 3  1.1210 3   0 3 2 3  3 3 3 3  3 3 3 3  3 3 3     0.2803 0   0 2 1 1  1 0 0 3  3 3 3 3  2 3 3  0.0561 0   0 0 0 0  0 0 0 0      1 3 3 3  0 3 2  0.0112 0   0 0 0 0  0 0 0 0  0 0 0 2  0 0 0  38 5.6050     3   0 3 3 3  3 3 3 3  3 3 3 3  3 3 3  1.1210 3   0 3 2 3  3 3 2 3  3 3 3     3  3 3 3  0.2803 0   0 3 2 2  2 3 1 3  3 3 3 3  3 3 3  0.0561 0   0 1 0     0  0 0 0 1  2 2 3 3  1 3 3  0.0112 0   0 0 0 0  0 0 0 0  1 0 1 1  0 0 0     40 5.6050 3   1 3 3 3  3 3 3 3  3 3 3 3  3 3 3  1.1210 2   0 3 2 3  3 3     2 3  3 3 3 3  3 3 3  0.5605 2   0 3 2 3  3 2 2 3  3 3 3 3  3 3 3  0.2803     2   0 3 1 3  3 2 2 3  3 3 3 3  2 3 3  0.1401 0   0 1 1 1  1 0 1 2  3 3 3     3  2 3 3  0.0701 0   0 0 1 1  0 0 1 2  3 3 3 3  1 0 3  0.0350 0   0 0 1     1  1 0 0 1  2 3 3 3  0 1 2  41 5.6050 3   2 3 3 3  3 3 3 3  3 3 3 3  3 3     3  1.1210 3   1 3 3 3  3 3 3 3  3 3 3 3  3 3 3  0.2803 1   0 3 3 2  2 0     1 3  3 3 3 3  3 3 3  0.0561 0   0 1 1 1  0 0 0 2  2 2 3 3  1 1 2  0.0112     1   0 N 0 0  0 0 0 0  2 1 2 3  0 0 0  42 5.6050 3   1 3 3 3  3 3 3 3  3     3 3 3  3 3 3  1.1210 2   0 3 3 3  3 3 3 3  3 3 3 3  3 3 3  0.5605 1   0     3 3 3  3 2 3 3  3 3 3 3  3 3 3  0.2803 0   0 3 1 2  3 2 1 2  3 3 3 3  3     3 3  0.1401 0   0 3 0 1  2 1 1 0  2 3 3 3  3 3 3  0.0701 0   0 1 0 0  2     0 1 1  0 3 3 3  3 3 3  0.0350 0   0 2 0 0  2 0 1 1  1 1 3 3  3 3 3   *     0.0175 0   0 0 0 0  0 0 0 0 0 0 2 1 1 3 0 2 3   * 0.0087 0   0 0 0 0  0     0 0 0 0 0 0 0 1 1 0 0 2  43 5.6050 3   1 3 3 3  3 3 3 3  3 3 3 3  3 3 3     1.1210 3   1 3 2 3  3 3 3 3  3 3 3 3  3 3 3  0.5605 2   0 2 1 3  3 1 2 3      2 3 3 3  3 3 3  0.2803 0   0 2 1 2  3 2 2 1  2 3 3 3  3 3 3  0.1401 0     0 3 0 0  2 0 2 1  2 3 3 3  3 3 3  0.0701 0   0 2 0 1  2 0 0 1  0 3 3 3     2 2 3  0.0350 0   0 0 0 1  2 0 0 0  0 3 3 3  1 2 2  0.0175 0   0 0 0 1     0 0 0 0  0 0 3 1  3 1 2  0.0087 0   0 0 0 0  0 0 0 0  0 0 2 1  1 0 1  44     5.6050 3   2 3 3 3  3 3 3 3  3 3 3 3  3 3 3  1.1210 3   1 3 3 3  3 3 3 3      3 3 3 3  3 3 3  0.5605 3   0 3 3 3  3 3 3 3  3 3 3 3  3 3 3  0.2803 1     0 3 2 1  3 3 3 3  3 3 3 3  3 3 3  0.1401 0   0 2 2 1  3 1 2 3  3 3 3 3     2 3 3  0.0701 0   0 1 0 0  3 0 2 3  0 3 3 3  2 3 3  0.0350 0   0 0 0 0     2 1 1 2  0 3 3 3  1 2 3  0.0175 0   0 0 0 0  0 0 0 0  0 3 0 3  0 2 1     0.0087 0   0 1 0 0  0 0 0 0  0 1 1 3  0 0 1  45 5.6050 3   3 3 3 3  3 3     3 3 3 3 3 3 3 3 3 3 3  1.1210 3   3 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3     0.5605 1   1 3 3 3  3 1 3 3 2 2 3 3 3 3 3 3 3  0.2803 0   1 2 2 2  3 1 3     3 1 2 3 3 3 3 2 3 3  0.1401 0   1 2 1 2  3 1 3 3 1 2 3 3 3 3 2 3 3     0.0701 0   1 2 0 1  1 0 0 0 0 1 2 3 3 3 2 3 2  0.0350 0   0 1 0 0  0 0 0     0 0 0 1 3 3 3 1 1 1  0.0175 0   0 1 0 0  0 0 0 0 0 1 0 0 3 3 1 0 0  46     5.6050 3   1 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 3   1 3 3 3  3 3 3     3 3 3 3 3 3 3 3 3 3  0.5605 2   1 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3     0.2803 0   0 2 2 3  3 2 3 3 3 3 3 3 3 3 3 3 3  0.1401 0   0 1 1 3  3 1 2     3 1 2 3 3 3 3 3 3 3  0.0701 0   0 1 1 2  1 1 3 2 1 1 3 3 3 3 2 3 3     0.0350 0   0 1 0 2  0 0 2 2 0 2 3 3 3 3 0 3 3  0.0175 0   0 0 0 0  0 0 1     0 0 0 2 3 3 3 1 2 2  0.0087 0   0 0 0 0  0 0 0 0 N 0 0 1 2 2 0 0 1  47     5.6050 2   0 3 3 3  3 2 2 3 2 3 3 3 3 3 3 3 3  1.1210 0   0 3 2 2  2 1 3     3 0 3 3 3 3 3 2 3 3  0.5605 0   0 2 3 3  2 0 2 3 0 2 3 3 3 3 1 3 3     0.2803 0   0 0 0 1  2 0 1 3 0 2 3 3 3 3 0 3 3  0.1401 0   0 0 0 0  0 0 0     3 0 0 0 3 2 3 0 0 1  0.0701 0   0 0 0 0  0 0 0 N 0 0 0 0 2 3 0 0 1     0.0350 0   0 0 0 0  0 0 0 N 0 0 0 0 1 0 0 0 0  0.0175 0   0 0 0 0  0 0 0     2 0 0 0 0 0 0 0 0 0  0.0087 0   0 0 0 0  0 0 0 N 0 0 0 0 0 0 0 0 0  48     5.6050 3   0 3 3 3  3 2 3 3 3 3 3 3 3 3 3 3 3  1.1210 3   0 3 3 3  3 2 2     3 3 3 3 3 3 3 3 3 3  0.5605 1   0 3 2 3  3 2 2 3 1 3 3 3 3 3 3 3 3     0.2803 0   0 2 2 3  3 1 1 3 1 3 3 3 3 3 2 3 3  0.1401 0   0 2 1 1  N 0 3     2 0 3 3 3 3 3 1 N 3  0.0701 0   0 2 0 1  1 0 0 1 0 2 3 3 3 2 1 0 2     0.0350 0   0 1 0 0  0 0 0 1 0 0 0 1 1 1 0 0 1  0.0175 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 N N 0  0.0087 0   0 1 0 0  0 0 0 0 0 0 0 0 0 0 0 N 0  49     5.6050 2   0 3 2 3  3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 0   1 3 1 1  2 2 0     3 1 2 3 3 3 3 3 3 3  0.5605 0   0 3 0 2  2 0 2 3 0 1 3 3 3 3 1 3 3     0.2803 0   0 1 0 0  1 0 1 2 0 0 3 2 3 3 0 1 2  0.1401 0   0 0 0 0  0 0 0     1 0 0 1 2 1 2 0 0 0

    TABLE B       0.0701 0   0 N 0 0  0 0 0 0 0 0 0 0 1 1 0 N 0  0.0350 0   0 0 0 0  0 0     0 0 0 0 0 0 0 0 0 0 0  0.0175 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  50     5.6050 3   2 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  0.1210 0   0 1 0 0  0 0 3     1 0 2 1 2 3 2 1 3 3  0.5605 0   0 2 0 0  2 0 3 2 0 2 2 3 3 3 0 3 3     0.2803 0   0 0 0 0  0 0 2 0 0 1 1 3 3 2 0 3 3  0.1401 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 0 1  0.0701 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0     0.0350 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  0.0175 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 0 0  51 5.6050 3   0 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3     1.1210 2   1 3 3 3  3 2 2 3 3 3 3 3 3 3 2 3 3  0.5605 0   1 2 2 3  3 0 3     3 1 2 3 3 3 3 2 3 3  0.2803 0   0 0 0 1  2 0 2 3 1 2 3 3 3 3 1 3 3     0.1401 0   0 0 1 2  2 0 1 3 0 2 3 3 3 3 0 N 2  0.0701 0   0 0 0 0  0 0 1     N 0 0 2 1 1 2 0 0 1  0.0350 0   0 1 0 0  0 0 0 N 0 0 1 1 1 2 0 0 0     0.0175 0   0 0 0 0  0 0 0 N 0 0 0 0 0 0 0 0 0  0.0087 0   0 0 0 0  0 0 0     2 0 0 1 0 0 0 0 0 N  52 5.6050 3   0 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3     1.1210 2   0 3 2 2  2 3 3 3 2 3 3 3 3 3 1 2 2  0.5605 0   0 3 2 1  1 0 3     1 1 3 3 3 3 3 2 3 2  0.2803 1   0 2 1 0  2 0 3 2 1 3 3 3 3 3 1 1 1     0.1401 0   0 0 0 0  0 0 1 1 0 2 3 2 3 3 0 0 0  0.0701 0   0 0 0 0  0 0 0     0 0 1 1 1 3 2 0 0 2  0.0350 0   0 0 0 0  0 0 0 0 0 0 0 0 3 0 0 0 0     0.0175 0   0 2 0 0  0 0 0 0 0 0 0 0 N 0 0 0 0  0.0087 0   0 2 0 0  0 0 0     0 0 0 0 0 0 0 0 0 0  53 5.6050 0   1 2 3 3  3 0 3 2 0 2 3 3 3 3 2 3 3     1.1210 0   0 0 0 0  0 0 0 0 0 0 0 0 1 2 0 2 2  0.5605 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 1 0  0.2803 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 1 0     0.1401 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  0.0701 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 0 0  54 5.6050 0   0 0 0 2  1 0 0 N 0 0 3 0 1 3 0 2 2     1.1210 0   0 0 0 0  0 0 0 N 0 0 1 0 0 2 0 0 0  0.5605 0   0 N 0 0  0 0 0     N 0 0 0 0 0 0 0 0 0  0.2803 0   0 0 0 0  0 0 0 N 0 0 0 0 0 0 0 0 0     0.1401 0   0 0 0 0  0 0 0 N 0 0 0 0 0 0 0 0 0  0.0701 0   0 0 0 0  0 0 0     N 0 0 0 0 0 0 0 0 0  0.0350 N   N N N N  N N N N N N N N N N N N N  55     5.6050 2   0 2 3 1  3 3 1 3 2 3 3 3 3 3 3 2 3  1.1210 0   0 1 2 1  0 0 0     3 1 1 3 3 1 3 1 0 2  0.5605 0   0 0 0 0  1 0 0 0 0 0 1 1 0 2 N N 1     0.2803 0   0 0 0 0  0 0 0 0 0 0 0 2 0 0 0 0 0  0.1401 0   0 0 0 0  0 0 0     0 0 0 1 0 0 0 0 0 0  0.0701 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0     0.0350 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  0.0175 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 0 0  0.0087 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  56     5.6050 2   0 3 3 3  3 3 3 3 1 2 3 3 3 3 3 3 3  1.1210 N   0 1 1 2  3 0 2     3 0 2 2 3 3 2 2 1 2  0.5605 0   0 0 0 0  0 0 0 0 0 1 3 2 3 0 1 0 1     0.2803 0   0 0 0 0  1 0 0 0 0 1 2 1 1 1 0 0 1  0.1401 0   0 0 0 0  0 0 0     0 0 0 1 0 0 0 0 0 0  0.0701 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0     0.0350 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  0.0175 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 0 0  57 5.6050 3   2 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3     1.1210 2   0 2 3 3  3 2 3 3 3 3 3 3 3 3 2 3 3  0.5605 3   0 3 3 3  3 2 2     3 1 3 3 3 3 3 3 3 3  0.2803 1   0 N 0 3  3 1 1 3 0 2 3 3 3 3 3 3 3     0.1401 1   0 2 0 3  3 2 2 3 1 2 3 3 3 3 2 3 3  0.0701 0   0 N 0 3  2 0 0     3 0 1 3 3 3 3 N 3 3  0.0350 0   0 2 0 2  2 0 1 3 N 0 3 3 3 3 0 0 2     0.0175 0   0 0 0 2  2 0 1 2 0 0 2 3 3 3 0 0 2  0.0087 0   N 0 0 0  0 0 0     0 0 0 1 2 2 2 0 0 0  58 5.6050 2   1 3 3 3  3 2 3 3 2 3 3 3 3 3 3 3 3     1.1210 0   0 2 0 1  3 1 3 3 1 3 3 3 3 3 3 3 3  0.5605 0   0 1 1 2  2 0 2     3 1 2 3 3 3 3 N 2 3  0.2803 0   0 0 0 0  1 0 1 2 0 2 2 3 3 1 0 0 1     0.1401 0   0 0 0 0  0 0 0 0 0 1 0 2 2 1 0 2 2  0.0701 0   0 0 0 0  0 0 0     0 0 0 0 1 2 0 0 0 0  0.0350 0   0 N 0 0  0 0 0 0 0 0 0 0 2 0 N 0 0     0.0175 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 1 N 0  59 5.6050 3   2 3 3 3  3     3 3 3 3 3 3 3 3 3 3 3 3  1.1210 1   0 3 1 3  3 2 3 3 2 3 3 3 3 3 3 3 3     0.5605 0   0 3 3 2  3 1 3 2 1 3 3 3 3 3 3 3 3  0.2803 0   0 2 1 1  1 0 3     1 1 2 3 3 3 3 3 3 3  0.1401 0   0 1 0 0  0 0 3 0 0 2 2 3 3 3 2 3 3     0.0701 0   0 0 0 0  1 0 2 0 0 2 2 2 3 3 0 3 3  0.0350 0   0 0 0 0  0 0 2     0 0 0 2 1 3 3 1 3 3  0.0175 0   0 N 0 0  0 0 1 0 0 0 0 0 2 2 0 3 1     0.0087 0   0 0 0 0  0 0 0 0 0 0 0 0 1 0 0 0 0  60 5.6050 3   1 3 3 3  3     3 3 3 3 3 3 3 3 3 3 3 3  1.1210 2   1 2 3 3  3 2 3 3 1 3 3 3 3 3 3 3 3     0.5605 0   0 1 1 1  2 1 3 3 1 2 3 3 3 3 2 3 3  0.2803 0   0 0 1 2  2 1 2     3 1 2 3 3 3 3 1 3 3  0.1401 0   0 1 0 1  2 0 2 1 0 0 3 3 3 3 1 2 2     0.0701 0   0 0 0 0  0 0 2 0 0 0 2 0 3 2 0 0 0  0.0350 0   0 0 0 0  0 0 1     1 0 0 3 3 3 3 0 0 2  0.0175 0   0 N 0 0  0 0 2 0 0 0 0 0 3 0 0 N 1     0.0087 0   0 0 0 0  0 0 0 0 0 0 0 0 0 1 0 2 0  61 5.6050 0   0 2 0 0  0     0 0 0 0 N 2 0 3 1 N 2 0  1.1210 0   0 1 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0     0.5605 0   0 1 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  0.2803 0   0 1 0 0  0 0 0     0 0 0 0 0 0 0 0 0 0  62 5.6050 3   2 3 3 3  3 3 3 3 2 3 3 3 3 3 3 3 3     1.1210 1   0 3 2 3  3 3 3 3 1 3 3 3 3 3 3 3 3  0.5605 0   0 2 0 3  3 1 2     3 1 2 3 3 3 3 1 3 3  0.2803 0   0 1 0 0  0 0 2 2 1 2 2 3 3 3 1 0 2     0.1401 0   0 1 0 0  2 0 2 3 0 2 3 3 3 3 1 1 3  0.0701 0   0 1 0 0  0 0 2     2 0 1 1 2 3 1 0 0 2  0.0350 0   0 1 0 0  0 0 1 3 0 0 3 3 2 3 0 0 1     0.0175 0   0 0 0 0  0 0 0 2 0 0 0 0 0 1 0 0 1  63 5.6050 0   0 2 1 3  3     0 2 2 1 0 3 3 3 3 3 3 2  1.1210 0   0 0 0 N  1 0 2 0 0 0 3 3 3 3 0 0 0     0.5605 0   0 0 0 0  0 0 1 0 0 0 0 1 3 2 0 0 0  0.2803 0   0 0 0 0  0 0 0     0 0 0 0 1 2 3 0 0 0  0.1401 0   0 0 0 0  0 0 0 0 0 0 0 0 0 1 0 0 0     0.0701 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  0.0350 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 0 0  0.0175 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  64     5.6050 3   3 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 2   0 3 3 3  3 3 3     3 3 3 3 3 3 3 2 3 3  0.5605 2   0 3 3 3  3 2 3 3 2 3 3 3 3 3 2 3 3     0.2803 1   0 1 1 2  2 3 3 3 2 3 3 3 3 3 1 2 3  0.1401 1   0 0 0 0  0 2 2     1 0 3 3 3 3 3 0 1 3  0.0701 0   0 0 0 0  0 0 1 1 0 2 3 3 3 3 0 0 2     0.0350 0   0 N 0 0  0 0 1 0 0 2 3 3 2 3 N N 2  0.0175 0   0 0 0 0  0 0 0     0 0 0 1 0 0 0 0 0 2  65 5.6050 3   2 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3     1.1210 0   0 3 2 3  3 3 3 3 1 3 3 3 3 3 2 3 3  0.5605 0   0 0 0 0  2 2 3     0 0 3 3 3 3 3 0 3 3  0.2803 0   0 0 0 0  0 0 1 0 0 3 3 3 3 3 0 2 2     0.1401 0   0 0 0 0  0 0 0 0 0 1 2 2 3 2 0 0 0  0.0701 0   0 0 0 0  0 0 0     0 0 0 0 0 3 0 0 0 0  0.0350 0   0 0 0 0  0 0 0 0 0 0 0 0 3 0 0 0 0  66     5.6050 3   3 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 3   1 3 3 3  3 3 3     3 3 3 3 3 3 3 3 3 3  0.5605 1   0 3 2 2  3 3 3 3 2 3 3 3 3 3 3 3 3     0.2803 2   0 3 N 2  2 3 3 3 1 3 3 3 3 3 3 3 3  0.1401 1   0 3 1 2  3 3 3     2 0 3 3 3 3 3 N 3 3  0.0701 0   0 3 2 3  3 3 3 2 0 3 3 3 3 3 3 3 3     0.0350 0   1 0 0 2  2 1 2 1 0 3 3 3 3 3 0 2 2  0.0175 0   0 1 1 1  2 0 0     0 0 1 3 3 3 3 0 2 2  0.0087 0   0 0 0 0  0 0 0 0 0 1 2 N 0 3 0 0 0  67     5.6050 3   1 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 0   0 3 2 2  3 3 3     3 2 3 3 3 3 3 3 3 3  0.5605 0   1 2 1 2  2 2 2 2 0 2 3 3 3 3 2 3 3     0.2803 0   0 0 1 1  1 0 0 1 0 3 2 3 3 3 0 2 2  0.1401 0   0 0 0 0  0 0 0     0 0 3 2 3 3 3 0 N 1  0.0701 0   0 0 0 0  0 0 0 1 0 2 0 2 3 1 0 1 1     0.0350 0   0 0 0 0  0 0 0 0 0 1 0 2 3 0 0 0 0  0.0175 0   0 0 0 0  0 0 0     0 0 1 0 0 3 0 0 1 0  68 5.6050 0   0 3 2 1  1 3 3 2 0 2 3 3 3 3 1 3 3     1.1210 0   0 1 0 0  0 1 1 1 0 2 0 3 2 3 0 1 0  0.5605 0   0 0 0 0  0 0 0     0 0 2 0 2 2 1 0 1 1  0.2803 0   0 0 1 1  1 0 0 0 0 2 0 1 0 0 0 3 2     0.1401 0   0 0 0 0  0 0 0 0 0 2 0 1 0 0 0 0 0  0.0701 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 0 0  69 5.6050 2   2 2 3 3  3 3 3 3 2 3 3 3 3 3 2 3 3     1.1210 0   1 0 0 0  1 3 3 1 0 3 3 3 3 3 0 1 1  0.5605 0   0 0 0 0  1 2 3     2 0 2 1 3 3 3 0 3 3  0.2803 0   0 0 1 0  1 0 0 1 0 2 0 3 3 2 0 1 2     0.1401 0   0 0 0 0  0 1 1 0 0 1 0 2 0 1 0 0 0  0.0701 0   0 N 0 0  0 0 0     0 0 1 0 0 0 0 N N 0  0.0350 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0     0.0175 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  70 5.6050 3   2 3 3 3  3     3 3 3 3 3 3 3 3 3 3 3 3  1.1210 0   0 0 0 1  1 0 3 1 1 3 3 3 3 3 1 3 3     0.5605 0   0 0 0 0  0 0 0 0 0 1 3 3 3 3 0 1 0  0.2803 0   0 0 0 0  0 0 0     0 0 2 3 3 3 3 0 0 0  0.1401 0   0 0 0 0  0 0 0 0 0 0 0 0 1 0 0 0 0     0.0701 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  0.0350 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 0 0  0.0175 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 0  71     5.6050 3   2 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 0   3 3 2 1  3 3 3     3 2 3 3 3 3 3 2 3 3  0.5605 0   0 0 1 1  2 3 3 3 0 3 3 3 3 3 2 3 3     0.2803 0   0 0 2 1  2 1 3 2 0 2 3 3 3 3 1 2 3  0.1401 0   0 0 0 0  2 1 2     3 0 1 3 3 3 3 1 1 1  0.0701 0   0 0 1 1  0 0 1 2 0 1 1 2 3 2 0 1 1     0.0350 0   1 0 0 0  0 0 0 0 0 0 0 2 3 1 0 0 N  0.0175 0   0 0 0 0  0 0 0     0 0 0 0 1 2 1 0 0 0  0.0087 0   0 0 0 0  0 0 0 0 0 0 0 1 0 1 0 0 0  72     5.6050 3   3 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 3   2 3 3 3  3 3 3     3 3 3 3 3 3 3 3 3 3  0.5605 2   1 2 2 3  3 3 3 3 3 3 3 3 3 3 3 3 3     0.2803 0   0 1 1 1  2 3 3 3 0 3 3 3 3 3 1 3 3  0.1401 0   0 2 1 2  2 3 3     3 0 3 3 3 3 3 1 3 3  0.0701 0   0 1 0 1  2 2 3 3 0 3 3 3 3 3 0 3 3     0.0350 0   0 0 0 1  1 1 3 1 0 1 3 3 3 3 0 2 1  0.0175 0   0 0 0 0  0 0 3     0 0 1 3 2 2 2 0 1 1  0.0087 0   0 0 0 0  0 0 1 0 0 0 3 3 3 3 0 1 1  73     11.2100  0   0 0 1 1  1 1 0 0 0 3 0 1 1 1 0 1 1  5.6050 0   0 0 0 0  0 0     0 0 0 0 0 1 1 0 0 1 1  2.8025 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 N N 0     1.1210 0   0 0 0 0  0 0 0 0 0 1 0 0 0 0 0 1 1  77 5.6050 1   1 3 2 2  3     3 3 3 2 3 3 3 3 3 3 3 3  1.1210 0   0 3 0 2  2 3 3 N 0 3 3 3 3 3 3 3 3     0.5605 0   0 3 1 3  2 3 3 3 0 3 3 3 3 3 3 3 3  0.2803 0   0 3 1 3  1 3 0     2 0 3 3 3 3 3 3 3 3  0.1401 0   0 1 0 2  1 0 0 1 0 3 3 3 3 3 3 3 3     0.0701 0   0 2 0 0  0 0 0 2 0 3 1 3 3 3 1 3 1  78 5.6050 3   1 3 3 3  3     3 3 3 3 3 3 3 3 3 3 3 3  1.1210 2   1 3 3 2  3 3 3 3 3 3 3 3 3 3 1 3 3     0.5605 3   1 3 3 2  2 2 3 3 2 3 3 3 3 3 2 3 2  0.2803 1   N 1 2 1  2 0 3     N 0 3 3 3 3 3 N 3 1  0.1401 1   0 0 3 1  0 0 3 3 0 3 3 3 3 3 0 0 0     0.0701 1   0 N 3 N  0 0 2 3 0 0 3 3 0 3 0 N 1  0.0350 0   N 0 3 1  0 0 1     1 0 0 2 2 0 2 0 0 0  0.0175 1   N 0 0 0  0 0 0 0 0 0 1 0 0 0 0 0 0     0.0087 0   0 N 0 0  0 0 1 0 0 0 0 0 0 0 0 N 0  79 5.6050 2   1 3 3 3  3     3 3 3 2 3 3 3 3 3 3 3 3  1.1210 2   N 3 1 3  3 2 1 3 0 1 3 3 3 3 3 3 3     0.5605 0   0 3 3 3  1 1 3 0 0 3 3 3 3 3 3 3 3  0.2803 0   0 3 0 1  0 0 2     0 0 2 3 3 3 3 3 3 1  0.1401 0   0 0 0 0  0 0 1 0 0 2 1 3 3 3 N 3 N     0.0701 0   0 N 0 0  0 0 0 0 0 2 2 1 3 3 0 3 0  0.0350 0   0 1 0 0  0 0 0     0 0 1 1 0 3 1 N 3 N  0.0175 0   0 0 0 0  0 0 N 0 0 N N 0 3 0 0 0 0  80     5.6050 3   2 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 3   3 3 3 3  3 3 3     3 3 3 3 3 3 3 3 3 3  0.5605 3   3 3 3 2  3 3 3 3 3 3 3 3 3 3 2 3 3     0.2803 2   3 3 3 1  3 2 3 3 2 2 3 3 3 3 2 3 3  0.1401 0   2 3 2 0  1 2 3     3 1 1 3 3 2 3 1 3 3  0.0701 0   0 3 3 0  0 0 3 3 1 N 3 3 N 3 0 3 2     0.0350 0   N 3 1 0  0 0 2 1 0 1 1 3 0 1 2 2 1  0.0175 0   0 1 1 1  0 0 0     0 0 0 0 0 0 2 1 N 1  0.0087 0   0 1 0 0  0 0 0 0 0 0 0 0 0 0 N 0 0  81     5.6050 3   0 1 3 3  3 2 3 3 3 3 3 3 3 3 3 3 3  1.1210 1   N 0 2 1  0 1 3     3 3 2 3 3 3 3 1 2 2  0.5605 N   N 0 N 1  0 0 3 3 3 1 3 3 3 3 0 0 1     0.2803 0   0 0 2 1  1 0 2 1 0 1 3 2 3 3 N 0 2  0.1401 0   1 0 N 0  0 0 3     0 0 0 0 0 3 0 0 0 N  0.0701 0   N 0 0 N  N 0 2 0 0 0 N 0 2 0 0 0 3     0.0350 N   0 0 0 0  0 0 0 0 0 0 1 0 1 0 0 0 1  0.0175 0   0 0 0 0  0 0 0     0 0 0 0 0 0 0 0 0 N  0.0087 0   N 0 0 1  1 0 0 0 0 1 1 0 1 0 0 0 N  82     5.6050 3   3 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 3   0 3 3 3  3 3 3     3 3 3 3 3 3 3 3 3 3  0.5605 3   0 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 3     0.2803 3   0 3 3 2  3 3 3 3 3 2 3 3 3 3 2 3 3  0.1401 2   1 3 3 3  3 0 3     3 1 3 3 3 3 3 2 3 3  0.0701 0   0 2 1 0  3 0 3 1 0 3 3 3 3 3 0 2 1     0.0350 0   N 0 2 0  1 0 3 0 0 1 3 3 3 3 0 N 1  0.0175 0   0 0 0 0  0 0 0     0 0 1 0 3 3 3 0 0 0  0.0087 0   0 N 0 N  N 0 0 0 0 0 0 3 0 3 0 N N  83     5.6050 0   0 N 0 2  3 1 3 3 0 3 3 3 3 3 3 3 3  1.1210 0   0 3 0 2  1 0 3     1 0 1 3 2 3 3 3 3 2  0.5605 0   0 2 0 2  0 0 1 0 0 1 3 3 2 3 0 3 3     0.2803 0   0 2 0 N  0 0 0 0 0 0 0 0 0 0 N 3 3  0.1401 0   0 0 N 0  0 0 0     0 0 0 0 0 1 0 0 0 1  0.0701 0   0 1 0 0  0 0 0 0 0 0 0 0 2 0 0 N 2     0.0350 0   0 0 0 0  0 0 0 0 0 2 N 0 0 0 0 0 0  0.0175 0   0 0 0 0  0 0 0     0 0 1 0 0 0 0 N 0 1  0.0087 0   1 1 0 N  N 0 0 0 0 N N 0 0 0 N 1 N  84     5.6050 3 0 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 1 0 2 0 3 3 2 3 3 2 3     3 1 3 3 3 3 3  0.2803 0 0 1 0 0 2 0 1 0 2 3 1 0 2 3 3 3 3  0.0701 N 0 0     N N 1 0 1 0 N N N 1 N 3 0 3 1  0.0175 N 0 0 N 0 0 0 0 0 1 0 0 0 1 0 1 1     1  85 11.2100  3 0 0 2 1 3 1 1 3 3 2 3 3 1 3 3 1 3  5.6050 3 N 0 2 N 3 N     0 3 3 N 3 3 N 3 3 N 3  1.1210 0 1 0 0 1 3 0 1 0 3 N 3 3 0 3 3 1 1  86     5.6050 1 0 0 0 2 2 0 1 2 1 3 3 3 3 3 3 3 3  1.1210 N N 0 0 1 1 0 1 0 1 1     2 1 2 3 1 3 3  0.2803 1 0 0 0 0 0 0 0 0 1 0 1 1 0 0 2 0 0  0.0701 0 0 0     0 0 0 0 0 0 1 1 1 N 0 0 0 0 0  87 5.6050 3 2 3 0 3 3 3 3 3 3 3 3 3 3 3 3     3 3  1.1210 0 0 2 0 3 1 2 3 0 1 3 1 1 3 3 3 3 3  0.2803 N 1 0 0 0 1 1 0     0 0 1 0 0 1 1 3 3 2  0.0701 0 0 0 0 0 0 N 0 0 0 0 0 0 1 0 0 0 0  0.0175     0 1 0 0 0 0 N 0 N 0 0 0 0 0 0 0 0 0  88 5.6050 3 0 3 0 3 3 3 3 3 2 3 3 3     2 3 3 3 3  1.1210 0 0 2 0 0 2 1 3 2 1 3 3 0 2 3 3 3 3  0.5605 0 0 0 0 0     0 1 2 0 1 3 0 0 0 3 N 3 N  0.2803 0 0 0 0 0 0 0 1 0 0 3 0 0 0 3 3 3 3     0.1401 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0  0.0701 0 0 0 0 0 0 0 0 0 0 0     0 0 0 0 N 3 N  89 11.2100  3 2 3 0 3 3 1 3 2 3 3 3 3 3 3 3 3 3  5.6050 3     2 3 0 3 3 1 2 3 3 3 3 3 3 3 3 3 3  1.1210 3 0 1 1 0 1 1 0 0 2 3 3 1 3 3     3 3 3  91@ 5.6050 2   0 3 3 3  3 1 3 3 3 3 3 3 3 3 3 3 N   @ 1.1210 0     0 2 3 1  0 0 3 3 1 3 3 3 3 3 1 0 N   @ 0.5602 0   0 0 1 0  0 0 N 2 0 1 2     3 3 3 0 0 N   @ 0.2803 0   0 0 1 0  0 0 3 0 0 0 1 1 2 1 0 0 N   @ 0.1401     0   0 0 0 N  0 0 3 0 0 0 0 N 0 1 0 0 N   @ 0.0701 0   0 0 0 0  0 0 0 0 0     0 0 0 0 0 0 0 N   @ 0.0350 0   0 0 0 0  0 0 0 0 0 0 0 0 0 0 0 0 N  92+     5.6050 3 1 3 N 3 3 3 3 3 3 3 3 3 3 3 3 3 3   + 1.1210 2 1 3 N 3 3 3 3 2     3 3 3 3 3 3 3 3 3   +  0.2803 0 1 0 N 1 1 0 2 0 1 3 2 0 2 3 3 3 3   +     0.0701 0 2 0 N 0 0 0 0 0 0 0 0 0 0 0 3 0 3    + 0.0175 0 0 0 N 0 0 0 0 0     0 0 0 0 0 0 0 1 0   + 0.0087 0 0 0 N N 0 0 0 0 0 N 0 0 0 N 0 0 0  94+     5.6050 3 2 3 N 3 3 3 3 3 3 3 3 3 3 3 3 3 3   + 1.1210 3 1 3 N 3 3 3 3 3     3 3 3 3 3 3 3 3 3   + 0.2803 3 0 2 N 3 3 1 3 1 2 3 3 2 3 3 3 3 3   +     0.0701 1 0 0 N 1 0 0 1 0 1 1 3 1 2 3 3 3 3   + 0.0175 0 0 0 N 0 0 0 0 0     1 0 0 0 0 0 1 3 1   + 0.0087 0 0 0 N N 0 0 N 0 0 1 1 0 0 0 0 3 0  95     5.6050 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3  1.1210 3 0 3 0 3 3 3 3 3 3 3     3 3 3 3 3 3 3  0.2803 1 1 3 0 2 0 3 3 3 3 3 3 3 3 3 3 3 3  0.0701 0 0 3     0 1 1 0 2 1 1 3 3 1 3 3 3 3 3  0.0175 0 0 0 0 0 0 0 0 0 3 2 1 0 1 2 0 1     0  0.0087 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0  0.0044 0 0 0 0 0 0 0 0 0     0 0 0 0 0 0 0 0 0  97 5.6050 0 0 3 1 3 1 3 3 2 3 3 3 0 3 3 3 3 3  1.1210     0 0 0 0 3 1 1 2 1 3 2 0 0 2 3 3 3 3  0.2803 0 0 0 0 0 0 0 1 0 0 0 0 0 1     1 1 3 2  0.0701 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 1  99 5.6050 0 0 0 0 3     0 0 1 1 2 0 3 1 3 3 3 3 3  1.1210 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 1 3     0.2803 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 100 5.6050 1 0 0 0 3 3 0 3 3     3 3 3 3 3 3 3 3 3  1.1210 0 0 0 N 0 0 0 0 1 1 0 1 2 0 3 1 3 1  0.2803 N     0 0 N 0 1 0 0 0 1 0 1 0 N 0 0 0 1  0.0701 0 0 0 N 0 0 0 0 0 1 0 0 1 0 0     0 0 1 101 5.6050 0 0 0 0 0 2 0 0 0 1 0 0 0 1 2 0 3 1  1.1210 1 0 0 0 0 0     0 0 0 0 0 0 0 0 0 N 0 2  0.2803 N 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0     0.0701 N 0 1 N N N 0 0 0 0 N 1 0 0 N 0 0 1 102+ 5.6050 3 0 3 N 3 3 3 3 3     3 3 3 3 3 3 3 3 3   + 1.1210 3 2 3 N 3 3 2 3 2 3 3 3 3 3 3 3 3 3   +     0.2803 1 0 0 N 3 0 0 3 1 1 3 1 1 2 3 3 3 3   + 0.0701 0 0 0 N 0 0 0 1 0     0 0 0 0 0 0 0 3 2   + 0.0175 0 0 0 N 0 0 0 0 0 0 0 0 0 0 0 0 1 0   +     0.0087 0 0 0 N 0 0 0 0 0 0 0 0 0 0 0 0 0 0 103@ 5.6050 3   0 3 3 3  3 3     3 3 3 3 3 3 3 3 3 3 N   @ 1.1210 2   0 3 3 3  3 3 3 3 3 3 3 3 3 3 3 3 N      @ 0.5605 1   0 1 3 3  1 2 3 3 0 2 3 3 3 3 3 3 N   @ 0.2803 0   0 1 3 3     0 1 3 3 1 0 2 3 3 3 3 3 N   @ 0.1401 1   0 0 3 3  0 0 3 0 0 1 3 3 3 3 3     3 N   @ 0.0701 0   1 0 0 1  0 0 0 0 0 0 0 3 1 1 1 1 N   @ 0.0350 0   0 0     N 1  0 0 0 0 0 0 0 0 2 0 1 0 N   @ 0.0175 0   0 N 0 0  0 0 0 0 0 0 0 0 0     0 0 N N 104@ 11.2100  0   2 1 1 0  0 1 3 0 0 1 1 3 3 2 3 3 N   @ 5.6050     0   N 0 N 0  0 0 1 0 0 0 1 3 3 3 0 1 N   @ 1.1210 0   N N 1 N  0 0 1 0 0     1 N 1 3 2 1 N N 105 11.2100  0   0 0 0 1  1 0 3 1 0 1 3 3 3 3 0 0 --     5.6050 0   0 1 0 1  0 0 3 1 0 1 2 3 3 3 N N --  1.1210 0   0 1 0 0  0 0     1 0 0 0 0 0 1 0 0 0 -- 106 5.6050 2 0 3 0 0 3 0 2 1 2 3 3 3 0 3 3 3 3     1.1210 0 0 0 0 0 1 0 2 0 1 3 1 0 0 0 3 3 2  0.5605 0 0 0 0 0 0 0 1 0 0 3     0 0 0 1 3 3 2  0.2803 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 1 0  0.1401 0 0 0     0 0 0 0 0 0 0 0 0 0 0 0 0 0 0  0.0701 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0     0  0.0351 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0  0.0175 0 0 0 0 0 0 0 0 0     0 0 0 0 0 0 0 0 0 107 5.6050 2 0 1 0 3 3 0 3 2 3 3 3 3 3 3 3 3 3  1.1210     0 0 0 0 3 0 0 1 1 3 3 3 3 3 3 3 3 3  0.5605 N 1 0 0 3 0 0 1 0 1 3 3 1 2     1 3 3 3  0.2803 0 0 0 0 1 0 0 N 0 0 2 2 0 0 0 1 0 3  0.1401 0 0 0 0 0 0     0 N 0 0 0 0 0 0 1 0 0 0 108 5.6050 3 0 3 0 3 3 3 3 3 3 3 3 3 3 3 3 3 3     1.1210 3 0 3 0 3 2 1 2 2 3 3 3 1 3 3 3 3 3  0.2803 0 0 1 0 1 0 1 1 2 2 1     3 1 3 3 2 3 3  0.0701 0 0 0 N 0 0 0 0 0 0 0 0 0 0 0 0 2 0  0.0175 0 0 0     0 0 0 0 0 0 0 0 0 0 0 0 0 0 0  0.0087 0 0 0 N N 0 0 N 0 N N 1 0 N 0 N N     N 111+ 5.6050 3 0 3 N 3 3 3 3 3 3 3 3 3 3 3 3 3 3   + 1.1210 3 0 3 N 3 3     2 3 3 3 3 3 3 3 3 3 3 3   + 0.2803 0 0 0 N 2 1 3 1 0 1 3 3 0 2 3 3 3 3     + 0.0701 N 0 0 N 0 0 0 0 1 0 1 0 1 0 0 0 3 1 112 5.6050 3 0 3 0 3 1 3 3     3 3 3 3 3 3 3 3 3 3  1.1210 2 0 2 0 3 1 3 3 3 3 3 3 3 3 3 3 3 3  0.2803     1 0 0 0 1 0 1 2 2 0 3 3 2 3 3 3 3 3  0.0701 0 0 1 0 0 0 0 0 0 0 0 0 0 0     1 3 3 1  0.0175 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0     *CHEZ REPLACING DOBR.      CHEAT GRASS REPLACING DOWNY BROME     @POOR PESW EMERGENCE     +COBU EMERGENCE AND RICE GROWTH VARIABLE     +COBU POOR THROUGHOUT TEST

POST-EMERGENT HERBICIDE EXAMPLES

Although as has been stated above the compounds of this inventionexhibit predominantly pre-emergence activity in greenhouse testing,nevertheless many of these compounds are active post-emergentherbicides. The post-emergent activity is best seen on younger plantstreated at the 11/2 to 2 leaf stage. In the tests which follow, largerand more developed plants were used.

The post-emergence herbicidal activity of compounds of this inventionwas demonstrated by greenhouse testing, and the results are shown in thefollowing Table C. The post-emergent herbicidal activity index used inTable C is as follows:

    ______________________________________                                        Plant Response       Index                                                    ______________________________________                                         0-24% inhibition    0                                                        25-49% inhibition    1                                                        50-74% inhibition    2                                                        75-99% inhibition    3                                                         100% inhibition     4                                                        Species not planted  -- or a blank                                            ______________________________________                                    

As was the case with the pre-emergence data, some of the compoundsinitially receive ratings for plant response directly as percentinhibition in ten percent increments. Where this is the case, thepercentage has been converted according to the scale above.

POST-EMERGENCE ACTIVITY ON WEEDS

Top soil was placed in pans having holes in the bottom and compacted toa depth of 0.95 to 1.27 cm. from the top of the pan. A predeterminednumber of seeds of each of several dicotyledonous and monocotyledonousannual plant species and/or vegetative propagules for the perennialplant species were placed on the soil and pressed into the soil surface.The seeds and/or vegetative propagules were covered with soil andleveled. The pans were then placed on a bench in the greenhouse andwatered as needed for germination and growth. After the plants reachedthe desired age (two to three weeks), each pan (except the control pans)was removed to a spraying chamber and sprayed by means of an atomizer.The spray solution or suspension contained about 0.4% by volume of anemulsifying agent and a sufficient amount of the candidate chemical togive an application rate of the active ingredient of 11.2 kg/ha whileapplying a total amount of solution or suspension equivalent to 1870L/Ha (200 gallons /acre). The pans were returned to the greenhouse andwatered as before and the injury to the plants as compared to those incontrol pans was observed at approximately 10-14 days (usually 11 days)and in some instances observed again at 24-28 days (usually 25 days)after spraying. These latter observations are designated by a "pound"sign (π) following the column of example numbers in the Table. The plantspecies used in this set of tests were the same as those used in thefirst set of pre-emergence tests, and the plant identifying codes arethe same as those shown for Table A.

                                      TABLE C                                     __________________________________________________________________________    Herbicide Primary Post, spectrums 25 and 90                                           Y A S D B M C V I W C C P R R                                                 e n e o y o o e n i a o e h h                                         Ex. Rate                                                                              n b j b g g b l m b t l s q j                                         No. kg/ha                                                                             s g g r r l u e u w h q w g g                                         __________________________________________________________________________     1  11.2100                                                                           0     0 2 1 0 0     N 1 0 0 0                                          2  11.2100                                                                           0     0 0 0 0 1     0 0 0 0 0                                          3  11.2100                                                                           0     0 2 2 2 2     1 0 2 0 0                                          4  11.2100                                                                           0     0 0 0 0 1     0 0 0 0 0                                          5  11.2100                                                                           0     0 1 0 0 1     1 N 1 0 0                                          6  11.2100                                                                           1     0 1 1 1 1     0 1 0 0 0                                          7  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                          8  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                          9  11.2100                                                                           0     --                                                                              0 0 0 0     0 40                                                                              0 0                                           10  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         11  11.2100                                                                           0     0 0 1 0 0     0 1 0 0 0                                         12  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         13  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         14  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         15  11.2100                                                                           0     0 1 1 1 0     0 0 0 0 0                                         16  11.2100                                                                           0     0 0 0 0 0     0 N 0 0 0                                         17  11.2100                                                                           0     0 1 0 1 0     0 1 1 0 0                                         18  11.2100                                                                           1     0 1 1 2 2     1 1 1 0 0                                         19  11.2100                                                                           0     0 0 1 0 0     0 1 0 0 0                                         20  11.2100                                                                           0     0 0 1 0 1     0 2 1 0 N                                         21  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         22  11.2100                                                                           0     0 0 0 0 0     0 3 0 0 0                                         23  11.2100                                                                           0     0 1 1 0 0     0 1 0 0 0                                         24  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         25  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         26  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         27  11.2100                                                                           0     1 1 1 1 1     --                                                                              1 0 0 0                                         28  11.2100                                                                           0     0 1 1 2 2     1 2 1 0 0                                         29  11.2100                                                                           0     0 0 1 N 1     0 0 0 0 0                                         30  11.2100                                                                           0     0 1 1 1 2     0 1 1 0 0                                         31  11.2100                                                                           1     0 0 1 0 1     1 N 1 1 2                                         32  11.2100                                                                           0     0 0 1 0 1     0 1 0 0 0                                         33  11.2100                                                                           0     0 0 0 0 0     0 N 0 0 0                                         34  11.2100                                                                           1     1 1 1 1 1     1 0 0 1 0                                         35  11.2100                                                                           1     1 1 1 0 1     0 0 0 1 0                                         36  11.2100                                                                           0     0 1 1 1 1     0 0 0 0 0                                         37  11.2100                                                                           0     0 1 1 0 1     0 0 0 0 0                                         38  11.2100                                                                           0     0 1 0 0 0     0 0 0 0 0                                         39  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         41  11.2100                                                                           0     0 1 1 1 1     0 0 0 0 N                                         42  11.2100                                                                           0     1 1 1 1 0     0 0 0 0 3                                         43  11.2100                                                                           0     0 0 3 2 1     0 2 1 0 3                                         44  11.2100                                                                           0     0 2 1 0 0     0 1 0 0 0                                         45  11.2100                                                                           0     --                                                                              0 1 1 1     0 4 0 0 0                                             11.2100                                                                           0     --                                                                              0 1 2 2     0 4 0 0 0                                         46  11.2100                                                                           1     --                                                                              0 0 1 1     0 0 0 0 1                                         47  11.2100                                                                           0     0 0 1 1 0     0 1 0 0 0                                         48  11.2100                                                                           0     0 0 0 1 0     0 0 0 0 0                                         49  11.2100                                                                           0     0 0 0 0 0     0 3 0 0 0                                         50  11.2100                                                                           0     0 0 2 1 0     0 0 0 0 0                                         51  11.2100                                                                           0     0 0 1 0 1     0 1 0 0 0                                         52  11.2100                                                                           0     0 0 0 0 0     0 1 0 0 0                                         53  11.2100                                                                           0     0 0 2 0 1     0 0 0 0 0                                         54  11.2100                                                                           0     0 0 0 0 0     0 1 0 0 0                                         55  11.2100                                                                           0     0 2 1 0 0     0 0 0 0 0                                         56  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         57  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         58  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         59  11.2100                                                                           0     0 2 1 1 0     0 0 0 0 0                                         60  11.2100                                                                           0     0 2 1 1 0     0 0 0 0 0                                         61  11.2100                                                                           0     0 1 0 0 0     0 0 0 0 0                                         62  11.2100                                                                           0     0 1 1 1 1     0 2 0 0 0                                         63  11.2100                                                                           0     0 2 0 1 0     0 2 0 0 0                                         64  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         65  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         66  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         67  11.2100                                                                           0     0 1 1 0 0     0 2 0 0 0                                         68  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         69  11.2100                                                                           1     0 1 1 0 0     0 1 0 0 0                                         70  11.2100                                                                           0     0 0 0 0 0     N 0 0 0 0                                         71  11.2100                                                                           0     0 0 0 0 0     0 1 0 0 0                                         72  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         73  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         74  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         75  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         76  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         77  11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                          78*                                                                              11.2100                                                                           0     0 1 0 0 0     0 N 0 0 0                                         79  11.2100                                                                           0     0 0 1 0 0     0 3 0 0 0                                          80 11.2100                                                                           0     0 1 1 1 1     0 3 0 0 0                                         81  11.2100                                                                           0     0 1 1 0 1     1 0 0 0 N                                         82  11.2100                                                                           0     0 1 1 0 0     0 --                                                                              0 0 0                                         83  11.2100                                                                           1     0 3 1 1 1     N 2 0 1 0                                         84  11.2100                                                                           0 0 0 0 0 1 0 1 2 2                                                   85  11.2100                                                                           0 0 0 0 0 0 0 1 1 2                                                   86  11.2100                                                                           0 0 0 0 0 0 0 0 1 0                                                   87  11.2100                                                                           0 0 2 0 2 2 2 2 2 2                                                    88@                                                                              11.2100                                                                           0     0 0 1 0 0     0 0 0 0 0                                          89+                                                                              11.2100                                                                           0     0 0 0 0 0     0 0 0 0 0                                         90  11.2100                                                                           0 0 2 0 2 0 0 1 0 0                                                   91  11.2100                                                                           0     0 0 1 1 1     0 3 2 1 0                                         92  11.2100                                                                           0 0 2 0 1 1 0 1 1 1                                                    93+                                                                              11.2100                                                                           0 0 2 0 2 2 2 2 2 2                                                   94  11.2100                                                                           0 0 2 0 2 2 0 2 1 2                                                   95  11.2100                                                                           0 0 2 0 2 2 2 2 1 2                                                   .sup. 96(                                                                         11.2100                                                                           0 0 0 0 2 2 2 2 2 1                                                   97  11.2100                                                                           0 0 0 0 0 0 1 1 1 1                                                   98  11.2100                                                                           0 0 2 0 2 2 1 1 1 2                                                   99  11.2100                                                                           0 0 0 0 2 0 0 1 1 1                                                   100 11.2100                                                                           0 0 0 0 0 0 0 1 1 1                                                   101 11.2100                                                                           0 0 0 0 0 0 0 0 1 1                                                   102 11.2100                                                                           0 0 2 0 2 2 0 2 1 2                                                   103 11.2100                                                                           0     0 0 0 1 0     0 0 N 0 0                                         104 11.2100                                                                           0     0 0 0 0 0     0 0 N 0 0                                         105 11.2100                                                                           0     0 0 1 0 0     0 0 N 0 0                                          106@                                                                             11.2100                                                                           0     0 0 1 0 0     0 1 0 0 0                                         107 11.2100                                                                           0 0 0 0 0 0 0 0 0 0                                                   108 11.2100                                                                           0 0 0 0 1 2 0 2 1 2                                                   .sup. 109)                                                                        11.2100                                                                           0 0 2 0 2 2 1 2 2 2                                                    110-                                                                             11.2100                                                                           0 0 2 0 2 2 0 2 2 2                                                   111 11.2100                                                                           0 0 2 0 2 1 0 2 1 2                                                   112 11.2100                                                                           0 0 2 0 2 2 2 1 2 2                                                   __________________________________________________________________________     *POOR LQ GERMINATION.                                                          DAMPING OFFLQ.                                                               @POOR SMARTWEED GERMINATION                                                   +POOR GERMINATIONSW                                                           +DAMPING OFF  IM, WB                                                          (DAMPING OFF - IM, WB                                                         )DAMPING OFF  IM, WB POOR GERMINATION CB                                      -DAMPING OFF  IM, WB POOR GERMINATIONCB                                  

POST-EMERGENCE ACTIVITY ON WEEDS AND CROPS

Compounds of this invention were tested for herbicidal activity on weedplants in the presence of crop plants according to the followingprocedure:

Topsoil (silt loam) is sieved through a screen having 1.27 cm openings.In some of the tests the soil was mixed with fertilizer (1225 g/cu. m of12/5/9 containing isobutylidene diurea), while in other tests thefertilizer was omitted. This mixture is steam sterilized and then placedin aluminum pans 6.985 cm deep having ten holes in the bottom each 0.635cm in diameter. The soil mixture is compacted to a depth of 1.27 cm.from the top of the pan. A predetermined number of seeds of each ofseveral dicotyledonous and monocotyledonous annual plant species and/orvegetative propagules for the perennial plant species are placed on thesoil and pressed into the soil surface. The seeds and/or vegetativepropagules are covered with 1.27 cm of a mixture of 50% topsoil and 50%of a mixture of Canadian sphagnum peat moss, vermiculite and a wettingagent. The pans are then placed on a capillary mat on a greenhouse benchand subirrigated as needed. After the plants reach the desired stage (9to 14 days, 1 to 3 true leaf stage), each pan (except the control pans)is removed to a spraying chamber and sprayed by means of an atomizer,operating at a spray pressure of 170.3 kPa (10 psig) at the applicationrates noted in Table D. In the spray solution is an amount of anemulsifying agent mixture (35% butylamine salt of dodecylbenzenesulfonicacid and 65% tall oil condensed with ethylene oxide in the ratio of 11mols of ethylene oxide/mol of tall oil) to give a spray solution orsuspension. The spray solution or suspension contains a sufficientamount of the candidate chemical in order to give application rates ofthe active ingredient corresponding to those shown in Table D belowwhile applying a total amount of solution or suspension equivalent to1870 L/Ha (200 gallons/acre). The pans are returned to the greenhouseand watered as before and the injury to the plants as compared to thecontrol pans is observed at approximately 10-14 days (usually 11 days)and in some instances observed again at 24-28 days (usually 25 days)after spraying. These latter observations are designated by a "pound"sign (#) following the column of example numbers in the Table.

In the following Table D the legends used to identify the plant speciesare the same as those used in the preceeding Table B.

                                      TABLE D                                     __________________________________________________________________________            S C R C W N H J V W R G C                                                     o o a o i o e i e h i r o o r y a       r                                                                             u                                                                             o                                                                             e                             Ex.                                                                              Rate b t p b b g s w l e c s r b m g c       f                                                                             b                                                                             l                                                                             s                             No.                                                                              kg/ha                                                                              e z e u w l e e e z e o n r i r g       t                                                                             e                                                                             q                                                                             w                             __________________________________________________________________________    18 5.6050                                                                             2     1 2 2 2   0 1 1 2 2 0 1 2 2 1 1 2 N                                5.6050                                                                             3     3 2 3 3   2 2 1 3 3 1 2 3 2       2                                                                             1                                                                             2                                                                             N                                5.6050                                                                             2 2 2 1 3 2 3 3 3 1 0 2 3 1 2 2 3       2                                5.6050                                                                             3 2 3 1 3 2 3 3 3 2 1 3 3 2 2 2 3       2                                1.1210                                                                             1     2 0 1 1   2 1 1 3 3 0 1 3 2       1                                                                             1                                                                             2                                                                             N                                1.1210                                                                             2 2 2 2 2 3 2 3 2 0 0 1 2 0 2 2 3       1                                1.1210                                                                             1     1 0 1 1   0 1 1 2 2 0 1 2 1       0                                                                             1                                                                             2                                                                             N                                1.1210                                                                             2 2 2 2 2 2 2 3 3 0 0 2 2 0 2 1 3       1                             18 0.5605                                                                             1     2 0 1 1   2 1 0 1 2 0 1 2 3       1                                                                             1                                                                             1                                                                             N                                0.5605                                                                             1     1 2 0 1   0 1 0                                                                             1 2 0 1 1 2 0       0                                                                             1                                                                             N                                0.2803                                                                             0     2 0 1 1   2 0 0 0 2 0 0 0 0       0                                                                             1                                                                             1                                                                             N                                0.2803                                                                             0     1 1 1 0   0 0 0 0 2 0 0 0 1       0                                                                             0                                                                             1                                                                             N                                0.2803                                                                             2 1 2 2 2 2 2 3 1 0 0 0 0 0 0 0 3       1                                0.2803                                                                             2 2 3 1 2 2 2 2 2 0 0 0 0 0 0 0 3       1                                0.1401                                                                             1     0 1 0 0   0 0 0 0 0 0 0 0 0       0                                                                             0                                                                             1                                                                             N                                0.1401                                                                             0     1 0 1 1   1 0 0 0 0 0 0 0 0       0                                                                             0                                                                             1                                                                             N                             18 0.0701                                                                             0 0 2 0 1 1 0 2 1 0 0 0 0 0 0 0 3       0                                0.0701                                                                             0     0 0 0 1   0 0 0 0 1 0 N 0 1       0                                                                             0                                                                             0                                                                             N                                0.0701                                                                             0 1 2 0 0 2 1 2 2 0 0 0 0 0 0 0 3       0                                0.070l                                                                             0     0 0 0 1   2 0 0 0 0 0 0 0 0       0                                                                             1                                                                             1                                                                             N                             36 5.2687                                                                             2 2 2 2 3 2 2 3 3 0 0 0 3 1 2 2 3       2                                5.2687                                                                             2 2 3 2 3 2 3 3 3 0 0 0 3 1 2 2 3       2                                1.1210                                                                             2 1 2 1 2 1 2 2 2 0 0 1 1 0 0 2 3       1                                1.1210                                                                             2 2 2 2 N 2 3 2 2 0 0 1 1 0 0 2 3       1                                0.2803                                                                             1 1 2 1 N 1 1 N 1 0 0 0 0 0 0 0 3       1                             36 0.2803                                                                             1 2 2 0 N 2 2 N 2 0 0 0 0 0 0 0 3       0                                0.0701                                                                             0 1 1 0 N 0 0 2 1 0 0 0 1 0 0 0 1       0                                0.0701                                                                             1 1 1 0 N 0 1 3 0 0 0 0 1 0 0 0 2       0                             43 5.6050                                                                             1     1 1 2 0   0 1 1 1   1 0 1 2       2                                                                             0                                                                             0                                1.1210                                                                             0     1 1 1 1   0 1 1 0   0 0 0 1       0                                                                             0                                                                             0                             44 5.3808                                                                             2 2 2 2 2 2 2 3 3 0 2 2 3 2 2 2 3       2                                5.3808                                                                             2 3 3 2 2 3 3 3 3 0 1 2 3 2 2 2 3       2                                1.1210                                                                             2 2 2 1 3 2 2 2 2 0 0 1 1 0 1 0 3       2                                1.1210                                                                             2 1 2 1 3 2 1 2 2 0 0 0 1 0 1 0 3       1                             44 0.2803                                                                             2 1 1 0 2 2 0 2 0 0 0 0 0 0 0 0 3       0                                0.2803                                                                             1 2 1 0 2 1 1 2 1 0 0 0 0 0 0 0 3       0                                0.0701                                                                             0 1 0 0 1 0 1 1 1 0 0 0 0 0 0 0 2       0                                0.0701                                                                             0 1 1 0 2 0 0 2 1 0 0 0 0 0 0 0 2       0                             83 11.2100                                                                            1     2 1 2 2   3 0 0 0 2 0 0 3 3       2                                                                             3                                                                             3                                                                             3                                11.2100                                                                            1     2 2 2 2   3 1 0 0 2 0 1 2 3       2                                                                             2                                                                             2                                                                             2                                5.6050                                                                             2     3 0 3 3   3 0 N 0 2 0 1 0 3       3                                                                             1                                                                             3                                                                             0                                5.6050                                                                             2     3 1 3 2   2 0 N 0 2 0 2 1 3       2                                                                             1                                                                             2                                                                             2                                2.8025                                                                             2     3 0 3 3   2 0 N 0 2 0 0 0 3       1                                                                             1                                                                             3                                                                             1                             83 2.8025                                                                             2     3 1 3 2   2 0 N 0 3 0 0 0 2       0                                                                             2                                                                             2                                                                             2                                1.1210                                                                             1     3 1 1 1   1 0 0 0 1 0 0 0 2       0                                                                             1                                                                             1                                                                             0                                1.1210                                                                             1     2 1 1 2   1 0 0 0 0 0 0 0 1       1                                                                             1                                                                             3                                                                             0                                0.5605                                                                             0     2 1 3 N   1 0 N 0 0 0 0 0 3       0                                                                             0                                                                             3                                                                             0                                0.5605                                                                             0     3 1 3 1   1 0 0 0 0 0 0 0 3       0                                                                             0                                                                             2                                                                             0                                0.2803                                                                             0     2 1 1 N   0 0 0 0 0 0 0 0 2       0                                                                             0                                                                             3                                                                             0                                0.2803                                                                             0     2 0 1 1   0 0 0 0 0 0 0 0 2       0                                                                             0                                                                             1                                                                             0                             __________________________________________________________________________

As can be seen from the data above, some of the compounds appear to bequite safe on certain crops and can thus be used for selective controlof weeds in these crops.

The herbicidal compositions of this invention, including concentrateswhich require dilution prior to application, may contain at least oneactive ingredient and an adjuvant in liquid or solid form. Thecompositions are prepared by admixing the active ingredient with anadjuvant including diluents, extenders, carriers, and conditioningagents to provide compositions in the form of finely-divided particulatesolids, granules, pellets, solutions, dispersions or emulsions. Thus, itis believed that the active ingredient could be used with an adjuvantsuch as a finely-divided solid, a liquid of organic origin, water, awetting agent, a dispersing agent, an emulsifying agent or any suitablecombination of these.

Suitable wetting agents are believed to include alkyl benzene and alkylnaphthalene sulfonates, sulfated fatty alcohols, amines or acid amides,long chain acid esters of sodium isothionate, esters of sodiumsulfosuccinate, sulfated or sulfonated fatty acid esters, petroleumsulfonates, sulfonated vegetable oils, ditertiary acetylenic glycols,polyoxyethylene derivatives of alkylphenols (particularly isooctylphenoland nonylphenol) and polyoxyethylene derivatives of the mono-higherfatty acid esters of hexitol anhydrides (e.g., sorbitan). Preferreddispersants are methyl, cellulose, polyvinyl alcohol, sodium ligninsulfonates, polymeric alkyl naphthalene sulfonates, sodium naphthalenesulfonate, and polymethylene bisnaphthalene sulfonate.

Wettable powders are water-dispersible compositions containing one ormore active ingredients, an inert solid extender and one or more wettingand dispersing agents. The inert solid extenders are usually of mineralorigin such as the natural clays, diatomaceous earth and syntheticminerals derived from silica and the like. Examples of such extendersinclude kaolinites, attapulgite clay and synthetic magnesium silicate.The wettable powders compositions of this invention usually contain fromabove 0.5 to 60 parts (preferably from 5-20 parts) of active ingredient,from about 0.25 to 25 parts (preferably 1-15 parts) of wetting agent,from about 0.25 to 25 parts (preferably 1.0-15 parts) of dispersant andfrom 5 to about 95 parts (preferably 5-50 parts) of inert solidextender, all parts being by weight of the total composition. Whererequired, from about 0.1 to 2.0 parts of the solid inert extender can bereplaced by a corrosion inhibitor or anti-foaming agent or both.

Other formulations include dust concentrates comprising from 0.1 to 60%by weight of the active ingredient on a suitable extender; these dustsmay be diluted for application at concentrations within the range offrom about 0.1-10% by weight.

Aqueous suspensions or emulsions may be prepared by stirring anonaqueous solution of a water-insoluble active ingredient and anemulsification agent with water until uniform and then homogenizing togive stable emulsion of very finelydivided particles. The resultingconcentrated aqueous suspension is characterized by its extremely smallparticle size, so that when diluted and sprayed, coverage is veryuniform. Suitable concentrations of these formulations contain fromabout 0.1-60% preferably 5-50% by weight of active ingredient, the upperlimit being determined by the solubility limit of active ingredient inthe solvent.

Concentrates are usually solutions of active ingredient inwater-immiscible or partially waterimmiscible solvents together with asurface active agent. Suitable solvents for the active ingredient ofthis invention include dimethylformamide, dimethylsulfoxide,N-methyl-pyrrolidone, hydrocarbons, and water-immiscible ethers, esters,or ketones. However, other high strength liquid concentrates may beformulated by dissolving the active ingredient in a solvent thendiluting, e.g., with kerosene, to spray concentration.

The concentrate compositions herein generally contain from about 0.1 to95 parts (preferably 5-60 parts) active ingredient, about 0.25 to 50parts (preferably 1-25 parts) surface active agent and where requiredabout 4 to 94 parts solvent, all parts being by weight based on thetotal weight of emulsifiable oil.

Granules are physically stable particulate compositions comprisingactive ingredient adhering to or distributed through a basic matrix ofan inert, finely-divided particulate extender. In order to aid leachingof the active ingredient from the particulate, a surface active agentsuch as those listed hereinbefore can be present in the composition.Natural clays, pyrophyllites, illite, and vermiculite are examples ofoperable classes of particulate mineral extenders. The preferredextenders are the porous, absorptive, preformed particules such aspreformed and screened particulate attapulgite or heat expanded,particulate vermiculite and the finelydivided clays such as kaolinclays, hydrated attapulgite or bentonitic clays. These extenders aresprayed or blended with the active ingredient to form the herbicidalgranules.

The granular compositions of this invention may contain from about 0.1to about 30 parts by weight of active ingredient per 100 parts by weightof clay and 0 to about 5 parts by weight of surface active agent per 100parts by weight of particulate clay.

The compositions of this invention can also contain other additaments,for example, fertilizers, other herbicides, other pesticides, safenersand the like used as adjuvants or in combination with any of theabove-described adjuvants. Chemicals useful in combination with theactive ingredients of this invention included, for example, triazines,ureas, carbamates, acetamides, acetanilides, uracils, acetic acid orphenol derivatives, thiolcarbamates, triazoles, benzoic acids, nitriles,biphenyl ethers and the like such as:

Heterocyclic Nitrogen/Sulfur Derivatives

2-Chloro-4-ethylamino-6-isopropylamino-s-triazine

2-Chloro-4,6-bis(isopropylamino)-s-triazine

2-Chloro-4,6-bis(ethylamino)-s-triazine

3-Isopropyl-1H-2,1,3-benzothiadiazin-4-(3H)-one 2,2 dioxide

3-Amino-1,2,4-triazole

6,7-Dihydrodipyrido(1,2-α:2',1'-c)-pyrazidiinium salt

5-Bromo-3-isopropyl-6-methyluracil 1,1'-Dimethyl-4,4'-bipyridinium

2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-3-quinolinecarboxylicacid

Isopropylamine salt of2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinic acid

Methyl 6-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-m-toluate andmethyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-p-toluate

Ureas N-(4-chlorophenoxy) phenyl-N,N-dimethylurea

N,N-dimethyl-N'-(3-chloro-4-methylphenyl) urea

3-(3,4-dichlorophenyl)-1,1-dimethylurea

1,3-Dimethyl-3-(2-benzothiazolyl) urea

3-(p-Chlorophenyl)-1,1-dimethylurea

1-Butyl-3-(3,4-dichlorophenyl)-1-methylurea

2-Chloro-N[(4-methoxy-6-methyl-3,5-triazin-2-yl)aminocarbonyl]-benzenesulfonamide

Methyl 2-(((((4,6-dimethyl-2-pyrimidinyl)amino)carbonyl)amino)sulfonyl)benzoate

Ethyl 2-[methyl2-(((((4,6-dimethyl-2-pyrimidinyl)amino)carbonyl)amino)sulfonyl)]benzoate

Methyl-2((4,6-dimethoxy pyrimidin-2-yl)aminocarbonyl)amino sulfonylmethyl) benzoate

Methyl2-(((((4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino)carbonyl)amino)sulfonyl)benzoate

Carbamates/Thiolcarbamates

2-Chloroallyl diethyldithiocarbamateS-(4-chlorobenzyl)N,N-diethylthiolcarbamate

Isopropyl N-(3-chlorophenyl) carbamate

S-2,3-dichloroallyl N,N-diisopropylthiolcarbamate

S-N,N-dipropylthiolcarbamate

S-propyl N,N-dipropylthiolcarbamate

S-2,3,3-trichloroallyl N,N-diisopropylthiolcarbamate

Acetamides/Acetanilides/Anilines/Amides

2-Chloro-N,N-diallylacetamide

N,N-dimethyl-2,2-diphenylacetamide

N-(2,4-dimethyl-5-[[(trifluoromethyl)sulfonyl]amino]phenyl]acetamideN-Isopropyl-2-chloroacetanilide

2',6'-Diethyl-N-methoxymethyl-2-chloroacetanilide

2'-Methyl-6'-ethyl-N-(2-methoxyprop-2-yl)-2-chloroacetanilideα,α,α-Trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine

N-(1,1-dimethylpropynyl)-3,5-dichlorobenzamide

Acids/Esters/Alcohols

2,2-Dichloropropionic acid

2-Methyl-4-chlorophenoxyacetic acid

2,4-Dichlorophenoxyacetic acid

Methyl-2-[4-(2,4-dichlorophenoxy)phenoxy]propionate

3-Amino-2,5-dichlorobenzoic acid

2-Methoxy-3,6-dichlorobenzoic acid

2,3,6-Trichlorophenylacetic acid

N-1-naphthylphthalamic acid

Sodium 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate

4,6-Dinitro-o-sec-butylphenol N-(phosphonomethyl) glycine and its salts.

Butyl 2-[4-[(5-(trifluoromethyl)-2-pyridinyl)oxy]phenoxy]-propanoate

Ethers 2,4-Dichlorophenyl-4-nitrophenyl ether

2-Chloro-α,α,α-trifluoro-p-tolyl-3-ethoxy-4-nitrodiphenyl ether

5-(2-chloro-4-trifluoromethylphenoxy)-N-methylsulfonyl 2-nitrobenzamide

1'-(Carboethoxy) ethyl5-[2-chloro-4-(trifluoromethyl)phenoxy-]2-nitrobenzoate

Miscellaneous 2,6-Dichlorobenzonitrile

Monosodium acid methanearsonate

Disodium methanearsonate

2-(2-chlorophenyl)methyl-4,4-dimethyl-3-isoxazolidinone

7-oxabicyclo (2.2.1) heptane, 1-methyl-4-(1-methylethyl)-2-(2-methylphenylmethoxy)-,exo-

Fertilizers useful in combination with the active ingredients include,for example ammonium nitrate, urea, potash and superphosphate. Otheruseful additaments include materials in which plant organisms take rootand grow such as compost, manure, humus, sand and the like.

Herbicidal formulations of the types described above are exemplified inseveral illustrative embodiments below.

    ______________________________________                                        I. Emulsifiable Concentrates                                                                       Weight Percent                                           ______________________________________                                        A.    Compound of Example No. 3                                                                          11.0                                                     Free acid of complex organic                                                                       5.59                                                     phosphate or aromatic or                                                      aliphatic hydrophobe base                                                     (e.g., GAFAC RE-610, registered                                               trademark of GAF Corp.)                                                       Polyoxyethylene/polyoxypropylene                                                                   1.11                                                     block copolymer with butanol                                                  (e.g., Tergitol XH, registered                                                trademark of Union Carbide Corp.)                                             Phenol               5.34                                                     Monochlorobenzene    76.96                                                                         100.00                                             B.    Compound of Example No. 14                                                                         25.00                                                    Free acid of complex organic                                                                       5.00                                                     phosphate of aromatic or                                                      aliphatic hydrophobe base                                                     (e.g., GAFAC RE-610)                                                          Polyoxyethylene/polyoxypropylene                                                                   1.60                                                     block copolymer with butanol                                                  (e.g., Tergitol XH)                                                           Phenol               4.75                                                     Monochlorobenzene    63.65                                                                         100.00                                             ______________________________________                                    

    ______________________________________                                        II. Flowables                                                                                     Weight Percent                                            ______________________________________                                        A.    Compound of Example No. 24                                                                        25.00                                                     Methyl cellulose    0.3                                                       Silica Aerogel      1.5                                                       Sodium lignosulfonate                                                                             3.5                                                       Sodium N-methyl-N-oleyl taurate                                                                   2.0                                                       Water               67.7                                                                          100.00                                              B.    Compound of Example No. 18                                                                        45.0                                                      Methyl cellulose    .3                                                        Silica aerogel      1.5                                                       Sodium lignosulfonate                                                                             3.5                                                       Sodium N-methyl-N-oleyl taurate                                                                   2.0                                                       Water               47.7                                                                          100.00                                              ______________________________________                                    

    ______________________________________                                        III. Wettable Powders                                                                             Weight Percent                                            ______________________________________                                        A.    Compound of Example No. 5                                                                         25.0                                                      Sodium lignosulfonate                                                                             3.0                                                       Sodium N-methyl-N-oleyl-taurate                                                                   1.0                                                       Amorphous silica (synthetic)                                                                      71.0                                                                          100.00                                              B.    Compound of Example 21                                                                            80.00                                                     Sodium dioctyl sulfosuccinate                                                                     1.25                                                      Calcium lignosulfonate                                                                            2.75                                                      Amorphous silica (synthetic)                                                                      16.00                                                                         100.00                                              C.    Compound of Example No. 6                                                                         10.0                                                      Sodium lignosulfonate                                                                             3.0                                                       Sodium N-methyl-N-oleyl-taurate                                                                   1.0                                                       Kaolinite clay      86.0                                                                          100.00                                              ______________________________________                                    

    ______________________________________                                        IV. Dusts                                                                                        Weight Percent                                             ______________________________________                                        A.    Compound of Example No. 13                                                                       2.0                                                        Attapulgite        98.0                                                                          100.00                                               B.    Compound of Example No. 10                                                                       60.0                                                       Montmorillonite    40.0                                                                          100.00                                               C.    Compound of Example No. 54                                                                       30.0                                                       Ethylene glycol    1.0                                                        Bentonite          69.0                                                                          100.00                                               D.    Compound of Example No. 62                                                                       1.0                                                        Diatomaceous earth 99.0                                                                          100.00                                               ______________________________________                                    

    ______________________________________                                        V. Granules                                                                                        Weight Percent                                           ______________________________________                                        A.    Compound of Example No. 52                                                                         15.0                                                     Granular attapulgite (20/40 mesh)                                                                  85.0                                                                          100.00                                             B.    Compound of Example No. 70                                                                         30.0                                                     Diatomaceous earth (20/40)                                                                         70.0                                                                          100.00                                             C.    Compound of Example No. 58                                                                         1.0                                                      Ethylene glycol      5.0                                                      Methylene blue       0.1                                                      Pyrophyllite         93.9                                                                          100.00                                             D.    Compound of Example No. 46                                                                         5.0                                                      Pyrophyllite (20/40) 95.0                                                                          100.00                                             ______________________________________                                    

When operating in accordance with the present invention, effectiveamounts of the compounds of this invention are applied to the soilcontaining the seeds, or vegetative propagules or may be incorporatedinto the soil media in any convenient fashion. The application of liquidand particulate solid compositions to the soil can be carried out byconventional methods, e.g., power dusters, boom and hand sprayers andspray dusters. The compositions can also be applied from airplanes as adust or a spray because of their effectiveness at low dosages.

The exact amount of active ingredient to be employed is dependent uponvarious factors, including the plant species and stage of developmentthereof, the type and condition of soil, the amount of rainfall and thespecific compounds employed. In selective preemergence application or tothe soil, a dosage of from about 0.02 to about 11.2 kg/ha, preferablyfrom about 0.1 to about 5.60 kg/ha, is usually employed. Lower or higherrates may be required in some instances. One skilled in the art canreadily determine from this specification, including the above examples,the optimum rate to be applied in any particular case.

The term "soil" is employed in its broadest sense to be inclusive of allconventional "soils" as defined in Webster's New InternationalDictionary, Second Edition, Unabridged (1961). Thus, the term refers toany substance or media in which vegetation may take root and grow, andincludes not only earth but also compost, manure, muck, humus, sand, andthe like, adapted to support plant growth.

Although the invention is described with respect to specificmodifications, the details thereof are not to be construed aslimitations.

We claim:
 1. A compound represented by the formula ##STR3## wherein: R₃is selected from the group consisting of 4,5-dihydro-2-oxazolyl and4,5-dihydro-2-thiazolyl; and the above mentioned heterocyclessubstituted with one or more substituents selected from lower alkyl,alkoxy and trifluoroacetyl;R₄ is selected from C₁ -C₄ straight orbranched chain alkyl, C₃ -C₄ cycloalkyl, cyclopropylmethyl,methylthiomethyl, and bis(methylthiomethyl; R₅ is the same as R₃ or is##STR4## or --C.tbd.N where Z₁ is selected from O and S, and Z₂ isselected from methoxy, ethoxy, 2-propenoxy, hydroxy, methylthio,cyanomethoxy, haloethoxy, methoxyethoxyethoxy, chloro, amino,methylamino, and dimethylamino; R₂ and R₆ are independently selectedfrom fluorinated methyl, chlorofluorinated methyl, chlorinated methyland lower alkyl, provided that one of R₂ and R₆ must be fluorinated orchlorofluorinated methyl.
 2. A compound according to claim 1 wherein oneof R₂ and R₆ is CF₃ and the other is CF₂ H.
 3. A compound according toclaim 2 wherein R₄ is selected from C₃ -C₄ branched chain alkyl.
 4. Acompound according to claim 2 wherein R₄ is selected from cyclobutyl andcyclopropylmethyl.
 5. A compound according to claim 3 wherein R₅ ismethoxycarbonyl.
 6. A compound according to claim 3 wherein R₅ ismethylthiocarbonyl.
 7. A compound according to claim 5 wherein R₃ is4,5-dihydro-2-thiazolyl.
 8. A compound according to claim 6 wherein R₃is 4,5-dihydro-2-thiazolyl.
 9. A compound according to claim 5 whereinR₃ is 4,5-dihydro-2-oxazolyl.
 10. A compound according to claim 6wherein R₃ is 4,5-dihydro-2-oxazolyl.
 11. A compound according to claim1 wherein one of R₂ and R₆ is CF₃ and the other is CF₂ Cl.
 12. Acompound according to claim 11 wherein R₄ is selected from C₃ -C₄branched chain alkyl.
 13. A compound according to claim 11 wherein R₄ isselected from cyclobutyl and cyclopropylmethyl.
 14. A compound accordingto claim 12 wherein R₅ is methoxycarbonyl.
 15. A compound according toclaim 12 wherein R₅ is methylthiocarbonyl.
 16. A compound according toclaim 14 wherein R₃ is 4,5-dihydro-2-thiazolyl.
 17. A compound accordingto claim 15 wherein R₃ is 4,5-dihydro-2-thiazolyl.
 18. A compoundaccording to claim 14 wherein R₃ is 4,5-dihydro-2-oxazolyl.
 19. Acompound according to claim 15 wherein R₃ is 4,5-dihydro-2-oxazolyl. 20.A method of controlling undesirable vegetation comprising applyingthereto an effective amount of a compound represented by the formula##STR5## wherein: R₃ is selected from the group consisting of4,5-dihydro-2-oxazolyl and 4,5-dihydro-2-thiazolyl; and the abovementioned heterocycles substituted with one or more substituentsselected from lower alkyl, alkoxy and trifluoroacetyl;R₄ is selectedfrom C₁ -C₄ straight or branched chain alkyl, C₃ -C₄ cycloalkyl,cyclopropylmethyl, methylthiomethyl, and bis(methylthiomethyl; R₅ is thesame as R₃ or is ##STR6## or --C.tbd.N where Z₁ is selected from O andS, and Z₂ is selected from methoxy, ethoxy, 2-propenoxy, hydroxy,methylthio, cyanomethoxy, haloethoxy, methoxyethoxyethoxy, chloro,amino, methylamino, and dimethylamino; R₂ and R₆ are independentlyselected from fluorinated methyl, chlorofluorinated methyl, chlorinatedmethyl and lower alkyl, provided that one of R₂ and R₆ must befluorinated or chlorofluorinated methyl.
 21. A method according to claim20 wherein one of R₂ and R₆ is CF₃ and the other is CF₂ H.
 22. A methodaccording to claim 21 wherein R₄ is selected from C₃ -C₄ branched chainalkyl.
 23. A method according to claim 21 wherein R₄ is selected fromcyclobutyl and cyclopropylmethyl.
 24. A method according to claim 22wherein R₅ is methoxycarbonyl.
 25. A method according to claim 22wherein R₅ is methylthiocarbonyl.
 26. A method according to claim 24wherein R₃ is 4,5-dihydro-2-thiazolyl.
 27. A method according to claim25 wherein R₃ is 4,5-dihydro-2-thiazolyl.
 28. A method according toclaim 24 wherein R₃ is 4,5-dihydro-2-oxazolyl.
 29. A method according toclaim 25 wherein R₃ is 4,5-dihydro-2-oxazolyl.
 30. A method according toclaim 20 wherein one of R₂ and R₆ is CF₃ and the other is CF₂ Cl.
 31. Amethod according to claim 30 wherein R₄ is selected from C₃ -C₄ branchedchain alkyl.
 32. A method according to claim 30 wherein R₄ is selectedfrm cyclobutyl and cyclopropylmethyl.
 33. A method according to claim 31wherein R₅ is methoxycarbonyl.
 34. A method according to claim 31wherein R₅ is methylthiocarbonyl.
 35. A method according to claim 33wherein R₃ is 4,5-dihydro-2-thiazolyl.
 36. A method according to claim34 wherein R₃ is 4,5-dihydro-2-thiazolyl.
 37. A method according toclaim 33 wherein R₃ is 4,5-dihydro-2-oxazolyl.
 38. A method according toclaim 34 wherein R₃ is 4,5-dihydro-2-oxazolyl.
 39. A herbicidalcomposition comprising an inert ingredient and an active ingredientrepresent by the formula ##STR7## wherein: R₃ is selected from the groupconsisting of 4,5-dihydro-2-oxazolyl and 4,5-dihydro-2-thiazolyl; andthe above mentioned heterocycles substituted with one or moresubstituents selected from lower alkyl, alkoxy and trifluoroacetyl; R₄is selected from C₁ -C₄ straight or branched chain alkyl, C₃ -C₄cycloalkyl, cyclopropylmethyl, methylthiomethyl, andbis(methylthiomethyl; R₅ is the same as R₃ or is ##STR8## or --C.tbd.Nwhere Z₁ is selected from O and S, and Z₂ is selected from methoxy,ethoxy, 2-propenoxy, hydroxy, methylthio, cyanomethoxy, haloethoxy,methoxyethoxyethoxy, chloro, amino, methylamino, and dimethylamino; R₂and R₆ are independently selected from fluorinated methyl,chlorofluorinated methyl, chlorinated methyl and lower alkyl, providedthat one of R₂ and R₆ must be fluorinated or chlorofluorinated methyl.40. A composition according to claim 39 wherein one of R₂ and R₆ is CF₃and the other is CF₂ H.
 41. A composition according to claim 40 whereinR₄ is selected from C₃ -C₄ branched chain alkyl.
 42. A compositionaccording to claim 40 wherein R₄ is selected from cyclobutyl andcyclopropylmethyl.
 43. A composition according to claim 41 wherein R₅ ismethoxycarbonyl.
 44. A composition according to claim 41 wherein R₅ ismethylthiocarbonyl.
 45. A composition according to claim 43 wherein R₃is 4,5-dihydro-2-thiazolyl.
 46. A composition according to claim 44wherein R₃ is 4,5-dihydro-2-thiazolyl.
 47. A composition according toclaim 43 wherein R₃ is 4,5-dihydro-2-oxazolyl.
 48. A compositionaccording to claim 44 wherein R₃ is 4,5-dihydro-2-oxazolyl.
 49. Acomposition according to claim 39 wherein one of R₂ and R₆ is CF₃ andthe other is CF₂ Cl.
 50. A composition according to claim 49 wherein R₄is selected from C₃ -C₄ branched chain alkyl.
 51. A compositionaccording to claim 49 wherein R₄ is selected from cyclobutyl andcyclopropylmethyl.
 52. A composition according to claim 50 wherein R₅ ismethoxycarbonyl.
 53. A composition according to claim 50 wherein R₅ ismethylthiocarbonyl.
 54. A composition according to claim 52 wherein R₃is 4,5-dihydro-2-thiazolyl.
 55. A composition according to claim 53wherein R₃ is 4,5-dihydro-2-thiazolyl.
 56. A composition according toclaim 52 wherein R₃ is 4,5-dihydro-2-oxazolyl.
 57. A compositionaccording to claim 53 wherein R₃ is 4,5-dihydro-2-oxazolyl.
 58. Thecompound 3-pyridinecarboxylic acid,4-(2-methylpropyl)-6-difluoromethyl-5-(4,5-dihydro-2-thiazolyl)-2-trifluoromethly-,methyl ester.
 59. The compound 3-pyridinecarboxylic acid,4-(2-methylpropyl)-2-difluoromethyl-5-(4,5-dihydro-2-thiazolyl)-6-trifluoromethyl-,methyl ester.